Aminopyridine Derivatives

ABSTRACT

The present invention provides compounds of formula (I): 
     
       
         
         
             
             
         
       
     
     compositions comprising such compounds; the use of such compounds in therapy (such as asthma or COPD); and methods of treating patients with such compounds; wherein R 1 -R 11  are as defined herein.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. patent application No. 61/071,431, filed Apr. 29, 2008, and Great Britain application number GB 0807828.9, filed Apr. 29, 2008, both of which are incorporated herein by reference in their entirety for all purposes.

This invention relates to aminopyridine derivatives and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives.

BACKGROUND OF THE INVENTION

The aminopyridine derivatives of the present invention are inhibitors of tissue kallikrein and have a number of therapeutic applications, particularly in the treatment of inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD).

The compounds of the invention are selective inhibitors of human tissue kallikrein (KLK1). In particular, they show an ability to inhibit KLK1 which is greater than their ability to inhibit other trypsin-like serine proteases.

Human tissue kallikrein, KLK1 (EC.3.4.21.35, also known as hK1, glandular kallikrein and urinary kallikrein) is a trypsin-like serine protease belonging to the kallikrein gene family of which there are 14 other members (including prostate specific antigen) (G. M. Yousef et al., Endocrine Rev., 2001, 22, 184). Other closely related trypsin-like serine proteases include plasma kallikrein, thrombin, trypsin and plasmin. Active KLK1 is a membrane-bound enzyme and is widely expressed. Strongest expression is observed in the pancreas, salivary gland, colon, kidney, lymph node, prostate, small intestine, stomach, thyroid gland and vagina. There is moderate expression of KLK1 in the lung, as well as expression in the saliva and its increased activity has also been detected in the sputum of patients following chronic lung injury.

KLK1 can liberate the kinins from kininogens by limited proteolysis, kallidin is released from low molecular weight kininogen whilst bradykinin is released from high molecular weight kininogen (K. D. Bhoola et al., Pharmacological Rev., 1992, 44, 1). Kinins such as kallidin (Lys-bradykinin) and bradykinin are potent mediators of inflammation. The actions of kinins are mediated by activation of two main bradykinin receptor subtypes, B1 and B2, both of which are members of the seven trans-membrane G protein-coupled receptor families. B1 receptors are involved in chronic responses and have low expression at basal levels but are upregulated following tissue injury and/or inflammation whilst B2 receptors are involved in acute responses and are constitutively expressed. KLK1 also activates the matrix metalloproteases (MMPs), pro-collagenase and pro-gelatinases and cleaves insulin-like growth factor binding protein-3 (J. A. Clements et al., Crit. Rev. Clin. Lab. Sci., 2004, 41, 265-312). There are also reports that KLK1 can directly activate the bradykinin receptors (C. Hecquet et al., Mol. Pharmacol., 2000, 39, 508-515).

Kinins have been shown to be important mediators in allergic inflammation such as asthma and hayfever (S. C. Chrstiansen et al., J. Clin. Invest., 1987, 79, 188-197) and that the enzyme chiefly responsible for the liberation of kinins in the airways of asthmatic subjects is KLK1 (S. C. Chrstiansen et al., Am. Rev. Respir. Dis., 1992, 145, 900-905). It has also been demonstrated that inflammatory cells release KLK1 (I. T. Lauredo et al., Am. J. Physiol. Lung Cell Mol. Physiol., 2004, 286, 734). Inhibition of KLK1 may be a novel approach for the treatment of asthma.

In addition KLK1 has been implicated in a number of other disease states including acute pancreatitis (T. Griesbacher, Pharmacology, 2000, 60, 113; T. Griesbacher et al., Br. J. Pharmacol., 2003, 139, 299), inflammatory bowel disease (A. Stadnicki, Digestive and Liver Disease, 2005, 37, 648; A. Stadnicki et al., Digestive Diseases and Science, 2003, 48, 615), arthritis (R. W. Colman, Immunopharmacology, 1999, 43, 103; R. J. Williams, Brit. J. Rheumatology, 1997, 36, 420).

High levels of circulating KLK1 induce chronic hypotension, Aprotinin a non-selective KLK1 inhibitor has been shown to suppress this (J. N. Sharma et al, Pharmacology, 1995, 50, 363; Q. Song et al., Immunopharmacology, 1996, 32, 105).

Antagonists of kinins (such as bradykinin receptor antagonists) have previously been investigated as potential therapeutic agents for the treatment of a number of inflammatory disorders (F. Marceau and D. Regoli, Nature Rev., Drug Discovery, 2004, 3, 845-852). In particular bradykinin B2 receptor antagonists have been investigated as potential treatments for airways disease (W. M. Abraham et al., Eur. J. Pharm., 2006, 533, 215).

There is also evidence that KLK1 plays a role in cancer (K. D. Bhoola et al., Curr. Opin. Invest. Drugs, 2007, 8, 462). KLK1 plays a role in increasing tumor invasiveness via activation of matrix metalloproteases, pro-collagenases and pro-gelatinases (K. D. Bhoola et al., Biol. Chem., 2001, 382, 77; H. Tschesche et al., Adv. Exp. Med. Biol., 1969, 247A, 545). Additionally KLK1 is indirectly involved in promoting proliferation through the liberation of mitogenic kinins (R. A. Roberts et al., J. Cell. Sci., 1989, 94, 527).

KLK1 is also involved in growth factor regulation and is implicated in processing of precursors of various growth factors e.g. EGF, NGF.

Endogenous inhibitors of KLK1 include the serpins, kallistatin, antiprotein C, α₁-antitrypsin, and α₁-antichymotrypsin. Aprotinin is also a potent non-selective KLK1 inhibitor. Low molecular weight inhibitors of KLK1 have previously been reported (M. Szelke et al., WO 199204371; M. Szelke et al., WO 199507291; C. Olivier et al., Peptides, 2000, 705; M. M. Staveski et al., WO 2003101941; M. Tokumasu et al., WO 2005095327; J. Burton et al., U.S. Pat. No. 5,464,820). KLK1 inhibitors have been reported to display activity in animal models of allergic inflammation (M. Szelke et al., Braz. J. Med. Biol. Res., 1994, 27, 1943; D. M. Evans et al., Immunopharmacology, 1996, 32, 117), citric acid induced cough (R. L. Featherstone et al., Lung, 1996, 174, 269) and acute pancreatitis (T. Griesbacher et al., Br. J. Pharmacol., 2002, 137, 692). KLK1 inhibitors have also been shown to be active in models of cancer (tumor cell migration in a matrigel invasion assay is inhibited in a dose-dependant manner by a KLK1 inhibitor) (W. C. Wolf et al., Am. J. Pathol, 2001, 159, 1797). A human KLK1 antibody that inhibits KLK1 with nanomolar potency has been shown to be active in an allergic sheep model of asthma. The antibody inhibited the late phase bronchoconstriction and completely blocked airway hyperresponsiveness (D. J. Sexton et al., WO 2006017538).

Hyaluronic acid which binds and inactivates KLK1 in vitro has been shown to block porcine pancreatic elastase induced bronchoconstriction in sheep (M. Scuri et al., Am. J. Respir. Crit. Care Med., 2001, 164, 1855).

Kallikrein-binding protein (KBP) is a serine protease inhibitor (serpin) which specifically binds to tissue kallikrein and inhibits kallikrein activity. KBP has been shown to inhibit retinal neovascularization and decrease vascular leakage by downregulation of vascular endothelial growth factor (VEGF) (G. Gao et al., Diabetologia, 2003, 46, 689) and to inhibit growth of gastric carcinoma by reducing VEGF production (L. Lu et al., Mol. Cancer. Ther., 2007, 6, 3297). VEGF has also been linked with blood-retinal barrier breakdown which is a hallmark of diabetic retinopathy (D. A. Antonettie et al., Diabetes, 1998, 47, 1953). VEGF has also been implicated in remodeling of airway vasculature in chronic inflammation (D. M. McDonald, Am. J. Respir. Crit. Care Med., 2001, 164, S39).

Selectivity with respect to the other members of the trypsin-like serine protease family, particularly plasma kallikrein, is an important issue. Inhibitors of tissue kallikrein displaying poor plasma kallikrein activity have previously been reported (M. Szelke et al., Brazilian J. Med. Biol. Res. 1994, 27, 1935 and D. M. Evans et al., Immunopharmacology, 1996, 32, 117), but there remains a need for further compounds that selectively inhibit tissue kallikrein. Several groups have disclosed synthetic inhibitors of plasma kallikrein. These include arginineketomethylene derivatives (WO 92/04371 and D. M. Evans et al., Immunopharmacology, 1996, 32, 115-116), noragmatine and agmatine derivatives (WO 95/07291, WO 94/29335), benzamidine derivatives (J. Sturzbecher et al., Brazilian J. Med. Biol. Res., 1994, 27, 1929-1934), boronic acid derivatives (U.S. Pat. No. 5,187,157) and aminomethylcyclohexanoyl derivatives (N. Teno et al., Chem. Pharm. Bull., 1993, 41, 1079-1090).

The compounds of the present invention, and their pharmaceutically acceptable salts, have the advantage that they are selective inhibitors of KLK1 (and so are likely to have reduced side effects). In addition, they may be more potent, they may be longer acting, they may have greater bioavailability or they may have other more desirable properties than the compounds of the prior art.

SUMMARY OF THE INVENTION

In one aspect, the present invention provides compounds of formula (I):

wherein:

R¹ and R² are independently selected from H, OH, (C₁-C₁₀)alkyl, (C₁-C₆)alkoxy, (C₂-C₆)alkenyl, (C₃-C₁₀)cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aryl(C₁-C₄)alkyl- and heteroaryl(C₁-C₄)alkyl-;

R³ is selected from H, (C₁-C₁₀)alkyl and (C₂-C₆)alkenyl;

R⁴ and R⁵ are selected from H, (C₁-C₁₀)alkyl, (C₂-C₆)alkenyl, (C₃-C₁₀)cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aryl(C₁-C₄)alkyl- and heteroaryl(C₁-C₄)alkyl-;

R⁶ and R⁷ are selected from H, (C₁-C₁₀)alkyl, (C₂-C₆)alkenyl, (C₃-C₁₀)cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aryl(C₁-C₄)alkyl-, aryl(C₂-C₄)alkenyl-, heteroaryl(C₁-C₄)alkyl-, —SO₂(C₁-C₆)alkyl, —SO₂aryl and —SO₂aryl(C₁-C₄)alkyl;

-   -   or R⁶ and R⁷ together with the nitrogen atom to which they are         attached may form a 4-7 membered N-containing ring, optionally         containing one further heteroatom selected from N, O and S, and         optionally substituted with 1 or 2 substituents independently         selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and         hydroxyl, said N-containing ring may also optionally be fused to         an aryl group;     -   or R⁴ and R⁶ together with the atoms to which they are attached         may form a saturated or partially unsaturated 4-7 membered         N-containing ring, optionally containing one further heteroatom         selected from N, O and S, and optionally substituted on carbon         with 1 or 2 substituents independently selected from         (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl;     -   or R⁵ is absent and R⁴ and R⁶ together with the atoms to which         they are attached may form a 5, 6, 9 or 10 membered mono- or         bi-cylic N-containing aromatic ring, optionally containing one         further heteroatom selected from N, O and S, and optionally         substituted on carbon with 1, 2 or 3 substituents independently         selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN, aryl,         COOR¹⁴ and hydroxyl;     -   or R⁴ and R⁶ may together form a group according to formula II         or formula III:

R⁸, R⁹ and R¹⁰ are independently selected from H, (C₁-C₁₀)alkyl, halogen, hydroxyl and (C₁-C₆)alkoxy;

R¹¹ is selected from H and (C₁-C₆)alkyl;

R¹² is selected from H and (C₁-C₆)alkyl;

R¹³ is selected from H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, OH, CN, CF₃, COOR¹⁴, halo and NR¹⁴R¹⁵;

R¹⁴ and R¹⁵ are independently selected from H and (C₁-C₆)alkyl;

f and g are independently selected from 0, 1, 2 and 3, such that f+g =1, 2 or 3;

h is selected from 1 and 2;

wherein:

-   -   alkyl may optionally be substituted with 1 or 2 substituents         independently selected from (C₃-C₁₀)cycloalkyl, (C₁-C₆)alkoxy,         OH, CN, CF₃, COOR¹⁴, halo and NR¹⁴R¹⁵;     -   alkenyl may optionally be substituted with 1 or 2 substituents         independently selected from (C₃-C₁₀)cycloalkyl, (C₁-C₆)alkoxy,         OH, CN, CF₃, COOR¹⁴, halo and NR¹⁴R¹⁵;     -   alkoxy may optionally be substituted with 1 or 2 substituents         independently selected from (C₃-C₁₀)cycloalkyl, OH, CN, CF₃,         COOR¹⁴, halo and NR¹⁴R¹⁵;     -   cycloalkyl is a non-aromatic mono- or bi-cylic hydrocarbon ring,         optionally fused to an aryl group, wherein said cycloalkyl ring         optionally contains, where possible, up to 2 double bonds; and         wherein, unless otherwise stated, said cycloalkyl may optionally         be substituted with 1 or 2 substituents independently selected         from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, OH, CN, CF₃, COOR¹⁴ , halo and         NR¹⁴R¹⁵;     -   heterocycloalkyl is a C-linked or N-linked 3 to 10 membered         non-aromatic, mono- or bi-cyclic ring, wherein said         heterocycloalkyl ring contains, where possible, 1, 2 or 3         heteroatoms independently selected from N, NR¹⁴, S(O)_(q) and O;         and said heterocycloalkyl ring optionally contains, where         possible, 1 or 2 double bonds, and is optionally substituted on         carbon with 1 or 2 substituents independently selected from         (C₁-C₆)alkyl, (C₁-C₆)alkoxy, OH, CN, CF₃, halo, COOR¹⁴, NR¹⁴R¹⁵         and aryl;     -   aryl is a single or fused aromatic ring system containing 6 or         10 carbon atoms; wherein, unless otherwise stated, each         occurrence of aryl may be optionally substituted with up to 5         substituents independently selected from (C₁-C₆)alkyl,         (C₁-C₆)alkoxy, OH, halo, CN, COOR¹⁴, CF₃ and NR¹⁴R¹⁵;     -   heteroaryl is a 5, 6, 9 or 10 membered mono- or bi-cyclic         aromatic ring, containing 1 or 2 N atoms and, optionally, an         NR¹⁴ atom, or one NR¹⁴ atom and an S or an O atom, or one S         atom, or one O atom; wherein, unless otherwise stated, said         heteroaryl may be optionally substituted with 1, 2 or 3         substituents independently selected from (C₁-C₆)alkyl,         (C₁-C₆)alkoxy, OH, halo, CN, COOR¹⁴, CF₃ and NR¹⁴R¹⁵;     -   q is 0, 1 or 2;

and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof.

In another aspect the present invention provides a prodrug of a compound of formula (I) as herein defined, or a pharmaceutically acceptable salt thereof.

In yet another aspect the present invention provides an N-oxide of a compound of formula (I) as herein defined, or a prodrug or pharmaceutically acceptable salt thereof.

It will be understood that certain compounds of the present invention may exist in solvated, for example hydrated, as well as unsolvated forms. It is to be understood that the present invention encompasses all such solvated forms.

In one subset of the compounds of formula (I):

R¹ is selected from (C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl, heterocycloalkyl, aryl and heteroaryl;

R² is selected from H, (C₁-C₆)alkyl, OH, (C₁-C₆)alkoxy, (C₃-C₁₀)cycloalkyl and aryl;

R³ is selected from H and (C₁-C₆)alkyl;

R⁴ is selected from H, (C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl, (C₃-C₁₀)cycloalkyl(C₁-C₄)alkyl-, aryl and aryl(C₁-C₄)alkyl-;

R⁵ is selected from H and (C₁-C₆)alkyl;

R⁶ is selected from H and (C₁-C₆)alkyl;

R⁷ is selected from H, (C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl, (C₃-C₁₀)cycloalkyl(C₁-C₄)alkyl-, aryl, heteroaryl, aryl(C₁-C₄)alkyl-, aryl(C₂-C₄)alkenyl-, heteroaryl(C₁-C₄)alkyl- and —SO₂(C₁-C₆)alkyl;

-   -   or R⁶ and R⁷ together with the nitrogen atom to which they are         attached may form a 4-7 membered N-containing ring, optionally         containing one further heteroatom selected from N, O and S, and         optionally fused to an aryl group;     -   or R⁴ and R⁶ together with the atoms to which they are attached         may form a 5 or 6 membered N-containing ring, optionally         containing one carbon-carbon double bond, and optionally         containing one further heteroatom selected from O and S, wherein         said N-containing ring is optionally substituted on carbon with         1 or 2 substituents independently selected from (C₁-C₆)alkyl,         halo, CN and hydroxyl;     -   or R⁵ is absent and R⁴ and R⁶ together with the atoms to which         they are attached may form a 5, 6 or 9 membered mono- or         bi-cyclic N-containing aromatic ring, optionally containing one         further heteroatom selected from N and O, and optionally         substituted on carbon with 1, 2 or 3 substituents independently         selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN, aryl,         COOR¹⁴ and hydroxyl;     -   or R⁴ and R⁶ may together form a group according to formula II         or formula III:

R⁸, R⁹ and R¹⁰ are indepently selected from H, (C₁-C₁₀)alkyl, halogen, hydroxyl and (C₁-C₆)alkoxy;

R¹¹ is selected from H and (C₁-C₁₀)alkyl;

R¹² is selected from H and (C₁-C₆)alkyl;

R¹³ is H;

f and g are independently selected from 0, 1, 2 and 3, such that f+g=1, 2 or 3;

h is selected from 1 and 2;

wherein alkyl, alkenyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are as defined above;

and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof.

The present invention also comprises the following aspects and combinations thereof:

In one aspect, the present invention provides a compound of formula (I) wherein R¹ is selected from (C₁-C₁₀)alkyl, (C₃-C₁₀)cycloalkyl, aryl, heteroaryl and aryl(C₁-C₄)alkyl-.

In another aspect, the present invention provides a compound of formula (I) wherein R¹ is selected from (C₁-C₆)alkyl, (C₅-C₁₀)cycloalkyl, aryl and heteroaryl.

In a further aspect, the present invention provides a compound of formula (I) wherein R¹ is selected from (C₅-C₁₀)cycloalkyl, aryl and heteroaryl.

In a yet further aspect, the present invention provides a compound of formula (I) wherein R¹ is optionally substituted phenyl. Optional substituents are selected from those defined above for ‘aryl’.

In one aspect, the present invention provides a compound of formula (I) wherein R² is selected from H, (C₁-C₆)alkyl, OH, (C₁-C₆)alkoxy, (C₃-C₁₀)cycloalkyl and aryl.

In another aspect, the present invention provides a compound of formula (I) wherein R² is selected from H, (C₁-C₆)alkyl, OH, (C₁-C₆)alkoxy and (C₃-C₁₀)cycloalkyl.

In yet another aspect, the present invention provides a compound of formula (I) wherein R² is selected from H, OH and (C₄-C₆)cycloalkyl.

In a further aspect, the present invention provides a compound of formula (I) wherein R² is H.

In one aspect, the present invention provides a compound of formula (I) wherein R³ is selected from H and (C₁-C₆)alkyl.

In another aspect, the present invention provides a compound of formula (I) wherein R³ is H.

In one aspect, the present invention provides a compound of formula (I) wherein R³ is H and the carbon atom to which R³ is attached is chiral and has an (S) configuration.

In another aspect, the present invention provides a compound of formula (I) wherein R³ is H and the carbon atom to which R³ is attached is chiral and has an (R) configuration.

In one aspect, the present invention provides a compound of formula (I) wherein R⁴ is selected from H, (C₁-C₁₀)alkyl, (C₃-C₁₀)cyclo alkyl, (C₃-C₁₀)cycloalkyl(C₁-C₄)alkyl-, aryl, heteroaryl, heteroaryl(C₁-C₄)alkyl- and aryl(C₁-C₄)alkyl-.

In another aspect, the present invention provides a compound of formula (I) wherein R⁴ is selected from (C₁-C₁₀)alkyl, (C₃-C₁₀)cycloalkyl, aryl, heteroaryl, heteroaryl(C₁-C₄)alkyl- and aryl(C₁-C₄)alkyl-.

In a further aspect, the present invention provides a compound of formula (I) wherein R⁴ is selected from H, (C₁-C₁₀)alkyl, (C₃-C₁₀)cycloalkyl, aryl and aryl(C₁-C₄)alkyl-.

In a yet further aspect, the present invention provides a compound of formula (I) wherein R⁴ is selected from H and (C₁-C₆)alkyl, (C₄-C₆)cycloalkyl, optionally substituted phenyl and optionally substituted phenyl(C₁-C₄)alkyl-. Optional substituents are selected from those defined above for ‘aryl’.

In one aspect, the present invention provides a compound of formula (I) wherein R⁵ is selected from H and (C₁-C₆)alkyl.

In another aspect, the present invention provides a compound of formula (I) wherein R⁵ is H.

In one aspect, the present invention provides a compound of formula (I) wherein one of R⁴ and R⁵ is H and the other of R⁴ and R⁵ is not H, and the carbon atom to which R⁴ and R⁵ is attached is chiral and has an (R) configuration.

In another aspect, the present invention provides a compound of formula (I) wherein one of R⁴ and R⁵ is H and the other of R⁴ and R⁵ is not H, and the carbon atom to which R⁴ and R⁵ is attached is chiral and has an (S) configuration.

In one aspect, the present invention provides a compound of formula (I) wherein R³ is H and the carbon atom to which R³ is attached is chiral and has an (R) configuration, and wherein one of R⁴ and R⁵ is H and the other of R⁴ and R⁵ is not H, and the carbon atom to which R⁴ and R⁵ are attached is chiral and has an (S) configuration.

In another aspect, the present invention provides a compound of formula (I) wherein R³ is H and the carbon atom to which R³ is attached is chiral and has an (S) configuration, and wherein one of R⁴ and R⁵ is H and the other of R⁴ and R⁵ is not H, and the carbon atom to which R⁴ and R⁵ are attached is chiral and has an (R) configuration.

In one aspect, the present invention provides compounds of formula (I) wherein R⁶ is selected from H, (C₁-C₁₀)alkyl, (C₃-C₁₀)cyclo alkyl, (C₃-C₁₀)cycloalkyl(C₁-C₄)alkyl-, aryl, aryl(C₁-C₄)alkyl- and —SO₂(C₁-C₆)alkyl.

In another aspect, the present invention provides compounds of formula (I) wherein R⁶ is selected from H and (C₁-C₆)alkyl.

In a further aspect, the present invention provides compounds of formula (I) wherein R⁶ is H.

In one aspect, the present invention provides compounds of formula (I) wherein R⁷ is selected from H, (C₁-C₁₀)alkyl, (C₃-C₁₀)cyclo alkyl, (C₃-C₁₀)cycloalkyl(C₁-C₄)alkyl-, aryl, heteroaryl, aryl(C₁-C₄)alkyl-, aryl(C₂-C₄)alkenyl-, heteroaryl(C₁-C₄)alkyl-, —SO₂(C₁-C₆)alkyl and —SO₂aryl.

In another aspect, the present invention provides compounds of formula (I) wherein R⁷ is selected from H, (C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl, aryl, heteroaryl, aryl(C₁-C₄)alkyl-, aryl(C₂-C₄)alkenyl-, heteroaryl(C₁-C₄)alkyl- and —SO₂(C₁-C₆)alkyl.

In a further aspect, the present invention provides compounds of formula (I) wherein R⁷ is selected from H, (C₁-C₆)alkyl, aryl, aryl(C₁-C₄)alkyl-, aryl(C₂-C₄)alkenyl-, heteroaryl(C₁-C₄)alkyl- and —SO₂(C₁-C₆)alkyl.

In a yet further aspect, the present invention provides compounds of formula (I) wherein R⁷ is selected from H, (C₁-C₆)alkyl, phenyl and phenyl(C₁-C₄)alkyl-.

In a still further aspect, the present invention provides compounds of formula (I) wherein R⁷ is selected from H and (C₁-C₆)alkyl.

In one aspect, the present invention provides compounds of formula (I) wherein R⁶ and R⁷ together with the nitrogen atom to which they are attached may form a 5-6 membered N-containing ring, optionally containing one further heteroatom selected from N, O and S, and optionally substituted with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl, said N-containing ring may also optionally be fused to an aryl group.

In another aspect, the present invention provides compounds of formula (I) wherein R⁶ and R⁷ together with the nitrogen atom to which they are attached may form a 5-6 membered N-containing ring, optionally containing one further heteroatom selected from O, and optionally substituted with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl, said N-containing ring may also optionally be fused to an aryl group.

In a further aspect, the present invention provides compounds of formula (I) wherein R⁶ and R⁷ together with the nitrogen atom to which they are attached may form a 5-6 membered N-containing ring, optionally containing one further heteroatom selected from O, and optionally fused to a phenyl group.

In a yet further aspect, the present invention provides compounds of formula (I) wherein R⁶ and R⁷ together with the nitrogen atom to which they are attached may form a 5-6 membered N-containing ring, optionally containing one further heteroatom selected from O, and optionally substituted with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl.

In a yet further aspect still, the present invention provides compounds of formula (I) wherein R⁶ and R⁷ together with the nitrogen atom to which they are attached may form a group selected from pyrolidinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, piperidinyl and morpholinyl, wherein each of said groups may optionally be substituted with 1, 2 or 3 substituents selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo and hydroxyl.

In one aspect, the present invention provides compounds of formula (I) wherein R⁴ and R⁶ together with the atoms to which they are attached may form a saturated or unsaturated 4-7 membered N-containing ring, optionally containing one further heteroatom selected from N, O and S, and optionally substituted on carbon with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl;

In another aspect, the present invention provides compounds of formula (I) wherein R⁴ and R⁶ together with the atoms to which they are attached may form a 4-7 membered N-containing ring, optionally containing one carbon-carbon double bond, optionally containing one further heteroatom selected from N, O and S, and optionally substituted on carbon with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl. Typically in this aspect, R⁵ is H and the carbon to which R⁴ and R⁵ are attached is chiral and has an (R) configuration.

In yet another aspect, the present invention provides compounds of formula (I) wherein R⁴ and R⁶ together with the atoms to which they are attached may form a 5 or 6 membered N-containing ring, optionally containing one carbon-carbon double bond, and optionally containing one further heteroatom selected from O and S, wherein said N-containing ring is optionally substituted on carbon with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, halo, CN and hydroxyl. Typically in this aspect, R⁵ is H and the carbon to which R⁴ and R⁵ are attached is chiral and has an (R) configuration.

In a further aspect, the present invention provides compounds of formula (I) wherein R⁵ is absent and R⁴ and R⁶ together with the atoms to which they are attached may form a 5, 6 or 9 membered N-containing mono- or bi-cyclic aromatic ring, optionally containing one further heteroatom selected from N and O, and optionally substituted on carbon with 1, 2 or 3 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, aryl, COOR¹⁴ and hydroxyl.

In a yet further aspect, the present invention provides compounds of formula (I) wherein R⁴ and R⁶ together with the atoms to which they are attached may form a group selected from pyrolidinyl, thiazolidinyl, tetrahydroisoquinolinyl, dihydro-1H-pyrrolyl, piperidinyl, pyrrolyl, imidazolyl, pyrazolyl, indolyl and benzimidazolyl, wherein each of said groups may optionally be substituted with 1, 2 or 3 substituents selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, aryl, COOR¹⁴ and hydroxyl.

In one aspect, the present invention provides compounds of formula (I) wherein R⁴ and R⁶ may together form a group according to formula II or formula III:

wherein R¹³ is H and f and g are independently selected from 0, 1, 2 and 3, such that f+g=1, 2 or 3; and h is selected from 1 and 2.

In one aspect, the present invention provides compounds of formula (I) wherein R⁸, R⁹ and R¹⁰ are independently selected from H, (C₁-C₁₀)alkyl and halogen.

In another aspect, the present invention provides compounds of formula (I) wherein R⁸, R⁹ and R¹⁰ are independently selected from H and (C₁-C₆)alkyl.

In a further aspect, the present invention provides compounds of formula (I) wherein R⁸, R⁹ and R¹⁰ are independently selected from H and methyl.

In a yet further aspect, the present invention provides compounds of formula (I) wherein one of R⁸, R⁹ and R¹⁰ is methyl and the other two are H.

In a yet further aspect still, the present invention provides compounds of formula (I) wherein R⁸, R⁹ and R¹⁰ are H.

In one aspect, the present invention provides compounds of formula (I) wherein R¹¹ is H.

In one aspect, the present invention provides compounds of formula (I) wherein R¹² is H.

In one aspect, the present invention provides a compound of formula (I) selected from:

(R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Benzyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-2-(Methanesulfonyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-(2-diethylamino-acetylamino)-3-(3,4-difluoro-phenyl)-propionamide;

(S)-2-Amino-3-methyl-pentanoic acid {(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide;

(S)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-3-(4-chloro-phenyl)-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-3-methyl-butyramide;

(R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide;

(R)-2-Amino-4-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide;

(S)-2-(2-Amino-acetylamino)-N-(6-amino-pyridin-3-ylmethyl)-3-(decahydro-naphthalen-1-yl)-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(decahydro-naphthalen-1-yl)-2-(2-methylamino-acetylamino)-propionamide;

(R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide;

(R)-2-Amino-N—{(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-3-methyl-butyramide;

(R)-Pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-phenyl-ethyl}-amide;

(R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

(R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-o-tolyl-ethyl}-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-cyano-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-2-yl-ethyl}-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-pentafluorophenyl-ethyl}-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-tert-butyl-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-phenyl-propionamide;

(R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(S)-Thiazolidine-4-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(S)-2-((R)-2-Amino-2-phenyl-acetylamino)-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide;

(S)-2-((S)-2-Amino-2-phenyl-acetylamino)-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-(4-chloro-phenyl)-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-3-phenyl-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3,3-dimethyl-butyramide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-propionamide;

(R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-1,2,3,4-Tetrahydro-isoquinoline-3-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-2,5-Dihydro-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-4,4-Difluoro-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-4-phenyl-butyramide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-cyclohexyl-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-(2-methylamino-acetylamino)-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-3-(4-chloro-phenyl)-propionamide;

(R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-Piperidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-ylethyl}-amide;

(R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide;

(R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

(R)-Piperidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-methylamino-acetylamino)-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-3-phenyl-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-methylamino-3-phenyl-propionamide;

(S)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(S)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-methylamino-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-methylamino-propionamide;

N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-methyl-2-methylamino-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-methylamino-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-methylamino-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-3-methyl-2-methylamino-butyramide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-pentafluorophenyl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-methoxy-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-phenyl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-tert-butyl-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-o-tolyl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-p-tolyl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-methoxy-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-fluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2,4-dichloro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-pyridin-4-yl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-quinolin-2-yl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide;

(S)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-o-tolyl-ethyl}-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-p-tolyl-ethyl}-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-methoxy-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-fluoro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2,4-dichloro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-pyridin-4-yl-ethyl}-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide;

(R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Propyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide

(R)-1-Isobutyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

{(R)-2-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethylcarbamoyl]-pyrrolidin-1-yl}-acetic acid methyl ester;

{(R)-2-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethylcarbamoyl]-pyrrolidin-1-yl}-acetic acid;

(R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-1-Ethyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

(R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

(R)-1-Propyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-1-Benzyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Benzyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-1-(4-Chloro-benzyl)-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-(3-Chloro-benzyl)-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(2R,4R)-4-Hydroxy-1-methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-2-Methyl-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-[2-(isopropyl-methyl-amino)-acetylamino]-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-[2-(benzyl-methyl-amino)-acetylamino]-3-(3,4-dichloro-phenyl)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-(2-dimethylamino-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-[2-(isobutyl-methyl-amino)-acetylamino]-propionamide;

(R)-2-(Isopropyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2-(isopropyl-methyl-amino)-acetylamino]-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-diisopropylamino-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-dipropylamino-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-diisobutylamino-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-phenethylamino-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2-(methyl-phenethyl-amino)-acetylamino]-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-{2-[methyl-((E)-3-phenyl-allyl)-amino]-acetylamino}-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-{2-[(4-chloro-benzyl)-methyl-amino]-acetylamino}-3-(3,4-difluoro-phenyl)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-{2-[(3-chloro-benzyl)-methyl-amino]-acetylamino}-3-(3,4-difluoro-phenyl)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-{2-[(2-chloro-benzyl)-methyl-amino]-acetylamino}-3-(3,4-difluoro-phenyl)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-{2-[(4-methoxy-benzyl)-methyl-amino]-acetylamino}-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-[2-(butyl-methyl-amino)-acetylamino]-3-(3,4-difluoro-phenyl)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2-(isobutyl-methyl-amino)-acetylamino]-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-[2-(cyclohexylmethyl-methyl-amino)-acetylamino]-3-(3,4-difluoro-phenyl)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-piperidin-1-yl-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-morpholin-4-yl-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-3,4-dihydro-1H-isoquinolin-2-yl-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-3,4-dihydro-2H-quinolin-1-yl-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2-(methyl-phenyl-amino)-acetylamino]-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(isobutyl-methyl-amino)-propionamide;

(R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-dimethylamino-3,3-dimethyl-butyramide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-dimethylamino-3,3-dimethyl-butyramide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-isopropylamino-3-phenyl-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-dimethylamino-3-phenyl-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-3-methyl-butyramide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide;

(2R)-3-Methyl-2-methylamino-pentanoic acid [(R)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-Pyrrolidine-2-carboxylic acid [(R)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(R)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(S)-Thiazolidine-4-carboxylic acid [(R)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-4,4-Difluoro-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(S)—N—[(R)-1-[(6-Amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-3-phenyl-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-(4-fluoro-phenyl)-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-(4-chloro-phenyl)-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-pyridin-3-yl-propionamide;

(R)—N-(6-Amino-2-methyl-pyridin-3-ylmethyl)-2-((S)-2-amino-2-phenyl-acetylamino)-3-(3,4-dichloro-phenyl)-propionamide;

(S)-2-((R)-2-Amino-2-cyclohexyl-acetylamino)-N-(6-amino-2-methyl-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide;

(R)-2-Amino-N—[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3,3-dimethyl-butyramide;

(R)-2-Amino-N—[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-cyclohexyl-propionamide;

(R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-1,2,3,4-Tetrahydro-quinoline-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2,4-dimethyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-2,4-dimethyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-2,4-dimethyl-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide;

(R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-5-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

(R)-1-Methanesulfonyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)-2-Methanesulfonylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-(methanesulfonyl-methyl-amino)-propionamide;

(R)-2-(Methanesulfonyl-methyl-amino)-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide;

(R)-2-Amino-3-methyl-pentanoic acid {(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide;

(S)-Pyrrolidine-2-carboxylic acid {(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide;

(S)-2-Amino-N—{(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-3-phenyl-propionamide;

(S)-2-Amino-N—{(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-3,3-dimethyl-butyramide;

(S)—N—{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-2-methylamino-propionamide;

(S)-3-Methyl-2-methylamino-pentanoic acid {(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide;

(R)-2-(2-Amino-acetylamino)-N-(6-amino-pyridin-3-ylmethyl)-3,3-dicyclohexyl-propionamide;

(R)—N-(6-Amino-pyridin-3-ylmethyl)-3,3-dicyclohexyl-2-(2-methylamino-acetylamino)-propionamide;

(R)—N-(6-Amino-pyridin-3-ylmethyl)-3,3-dicyclohexyl-2-(2-dimethylamino-acetylamino)-propionamide;

(S)-1-Methyl-pyrrolidine-2-carboxylic acid {(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide;

(S)-2-Amino-3-methyl-pentanoic acid {(1R,2R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-hydroxy-2-phenyl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-phenyl-ethyl}-methyl-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

1H-Pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide;

1H-Pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

1H-Pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

3,4,5-Trimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-phenyl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(;6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-o-tolyl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-pentafluorophenyl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-biphenyl-4-yl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-p-tolyl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-methoxy-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-ethoxy-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-tert-butyl-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-quinolin-2-yl-ethyl}-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-trifluoromethyl-phenyl)-ethyl]-amide;

4-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

4-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2,5-dichloro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-fluoro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-trifluoromethyl-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide;

5-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethylcarbamoyl]-1H-pyrrole-2-carboxylic acid methyl ester;

5-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethylcarbamoyl]-1H-pyrrole-2-carboxylic acid;

5-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethylcarbamoyl]-4-methyl-1H-pyrrole-2-carboxylic acid;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

1H-Imidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

1H-Imidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

1H-Imidazole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

1-Methyl-1H-imidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

2,5-Dimethyl-2H-pyrazole-3-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

5-p-Tolyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

5-p-Tolyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide;

5-p-Tolyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

5-p-Tolyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide;

5-p-Tolyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

5-p-Tolyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

1H-Benzoimidazole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

5-Methoxy-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

5-Fluoro-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

5-Hydroxy-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

5-Methoxy-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

5-Fluoro-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

1-Methyl-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid [(R)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

5-Methoxy-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide; 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

5-Fluoro-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

1H-Benzoimidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-pentafluorophenyl-ethyl}-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

5-Fluoro-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

1H-Benzoimidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-methoxy-phenyl)-ethyl]-amide;

1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide;

1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide;

5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide;

1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide;

(S)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-methyl-2-methylamino-butyramide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-3-methyl-2-methylamino-butyramide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-2-methylamino-3-phenyl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(cyclohexylmethyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-dimethylamino-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(methyl-propyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(butyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-3-methyl-butyramide;

(S)-2-(Isopropyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-diisopropylamino-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-dimethylamino-3-phenyl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-3-phenyl-propionamide;

(S)-2-(Isopropyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-diethylamino-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-pyrrolidin-1-yl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-pyrrolidin-1-yl-propionamide;

(R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-dimethylamino-3-methyl-butyramide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-3-hydroxy-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-3-hydroxy-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-diethylamino-3-hydroxy-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-diethylamino-3-hydroxy-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-3-diethylamino-succinamic acid methyl ester;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2-(2,6-dimethyl-piperidin-1-yl)-acetylamino]-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-pyrrolidin-1-acetylamino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-(methyl-propyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-(butyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-3-methyl-butyramide;

(S)-2-(Isopropyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-diisopropylamino-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2(isopropyl-methyl-amino)-3-phenyl-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-2-diethylamino-propionamide;

(R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-[2-(2,6-dimethyl-piperidin-1-yl)-acetylamino]-3-(4-fluoro-phenyl)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(4-fluoro-phenyl)-2-(2-piperidin-1-yl-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-(2-diethylamino-acetylamino)-3-(4-fluoro-phenyl)-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-(isopropyl-methyl-amino)-propionamide;

(S)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-(methyl-propyl-amino)-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-(ethyl-methyl-amino)-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-dipropylaminopropionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-dimethylamino-3-hydroxy-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-(ethyl-methyl-amino)-3-hydroxy-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-3-hydroxy-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-diethylamino-3-hydroxy-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-diethylamino-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-dimethylamino-propionamide;

(S)—N—(6-Amino-pyridin-3-ylmethyl)-3-cyclohexyl-2-[2-(2,6-dimethyl-piperidin-1-yl)-acetylamino]-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-cyclohexyl-2-(2-diisopropylamino-acetylamino)-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(decahydro-naphthalen-1-yl)-2-(2-diisopropylamino-acetylamino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-2-dimethylamino-3-phenyl-propionamide;

(R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-dimethylamino-3-methyl-butyramide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-dimethylamino-3-phenyl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-(2-piperidin-1-yl-acetylamino)-propionamide;

(R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-2-dimethylamino-3-methyl-butyramide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-2-dimethylamino-3-phenyl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-2-diethylamino-propionamide;

N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3-chloro-phenyl)-2-(2-piperidin-1-yl-acetylamino)-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-2-(ethyl-methyl-amino)-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-2-diethylamino-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-2-diethylamino-propionamide;

N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-(2-piperidin-1-yl-acetylamino)-3-(3-trifluoromethyl-phenyl)-propionamide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-trifluoromethyl-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-trifluoromethyl-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-2-(2-piperidin-1-yl-acetylamino)-3-(4-trifluoromethyl-phenyl)-propionamide;

(R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide;

N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(4-chloro-phenyl)-2-[2-(2,6-dimethyl-piperidin-1-yl)-acetylamino]-propionamide;

(S)-2-[(S)-2-(Isopropyl-methyl-amino)-propionylamino]-4-methyl-pentanoic acid (6-amino-pyridin-3-ylmethyl)-amide;

(S)—N-(6-Amino-2-methyl-pyridin-3-ylmethyl)-2-(2-diethylamino-acetylamino)-3-(4-fluoro-phenyl)-propionamide;

(S)—N-(6-Amino-2-methyl-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2-(2,6-dimethyl-piperidin-1-yl)-acetylamino]-propionamide;

(S)—N-(6-Amino-2-methyl-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-piperidin-1-yl-acetylamino)-propionamide;

(R)—N—[(S)-1-[(6-Amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N—[(S)-1-[(6-Amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide;

(S)—N—{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-2-dimethylamino-propionamide;

(S)—N—{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-2-hydroxy-ethyl}-2-(isopropyl-methyl-amino)-propionamide;

(R)—N-(6-Amino-pyridin-3-ylmethyl)-3-cyclohexyl-2-[(S)-2-(isopropyl-methyl-amino)-propionylamino]-butyramide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-(isopropyl-methyl-amino)-N-methyl-propionamide;

S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-diethylamino-N-methyl-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-dipropylamino-propionamide;

and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof.

In another aspect, the present invention provides a compound of formula (I) selected from:

(R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Propyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Isobutyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-diisopropylamino-acetylamino)-propionamide;

(R)-1-Methyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-dimethylamino-3,3-dimethyl-butyramide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

(R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

(S)-1-Methyl-pyrrolidine-2-carboxylic acid {(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide;

3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide;

3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-methyl-2-methylamino-butyramide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-diethylamino-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-diethylamino-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide;

(R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-dimethylamino-3-methyl-butyramide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-2-(isopropyl-methyl-amino)-propionamide;

(S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide;

and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof.

The skilled person will appreciate that each of the compounds identified above, or identified in the Examples provided herein below, taken alone or with any combination of the other identified compounds represents an independent aspect of the invention.

Therapeutic Applications

As previously mentioned, the compounds of the present invention have a number of therapeutic applications, particularly in the treatment of inflammatory diseases such as asthma and COPD, by virtue of their ability to inhibit KLK1.

In particular, the compounds of the present invention may be used for the treatment of respiratory disorders involving airways inflammation e.g. asthma (allergic and non-allergic) including exacerbations resulting from asthma and chronic obstructive pulmonary disease (COPD). Such compounds may also be used to treat other forms of allergic inflammation including allergic rhinitis (hayfever), rhino-conjunctivitis, rhinorrhoea, urticaria, excess lung mucus production and ascites build-up.

Other inflammatory disorders that may be treated with the compounds of the present invention include, multiple sclerosis, arthritis, rheumatoid arthritis, osteopathic arthritis, osteoarthritis, rhinitis, sinusitis, inflammatory bowel disease (such as Crohn's disease and ulcerative colitis), immune mediated diabetes, acute pancreatitis and interstitial cystitis, thermal injury, crush injury, conjunctivitis, periodontal disease, chronic prostate inflammation, chronic recurrent parotitis, inflammatory skin disorders (e.g. psoriasis, eczema), hepatic cirrhosis, spinal cord trauma and SIRS (systemic inflammatory response syndrome); smooth muscle spasm (e.g. asthma, angina), RDS (respiratory distress syndrome); hypotension (e.g. shock due to haemorrhage, septicaemia or anaphylaxis, carcinoid syndrome, dumping syndrome); oedema (e.g. burns, brain trauma, angioneurotic oedema whether or not as a result or treatment with inhibitors of angiotensin converting enzyme); pain and irritation (e.g. burns, wounds, cuts, rashes, stings, insect bites), migraine; male contraceptive agents by virtue of inhibition of prostate kallikrein; prevention of excessive blood loss during surgical procedures.

The compounds of the present invention may also be used to treat disorders that can be a response to the release of an inflammatory mediator (e.g. cough).

The compounds of the present invention may also be used to treat disorders involving regulation of growth factors (e.g. vascular endothelial growth factor (VEGF)) which may involve increased vascular permeability (e.g. diabetic retinopathy and septic shock).

The compounds of the present invention may be used to treat a neoplastic disorder (e.g. metastatic pancreatic adenocarcinomas, tumour angiogenesis) in particular they may be used to reduce angiogenesis associated with neoplasms e.g. cancer and tumour growth and to modulate angiogenesis and other processes associated with neoplasia and tumour growth and in particular may be used to block tumour angiogenesis and/or cancer cell invasion and metastasis.

Asthma

Asthma is a chronic lung condition that may be classified as allergic (intrinsic) or non-allergic (extrinsic). Patients with asthma experience difficulty breathing as a result of narrowing or obstruction of the airway, making it more difficult to move air in and out. This narrowing can result from airway inflammation and bronchoconstriction, Symptoms of asthma include, for example, wheezing, shortness of breath, bronchoconstriction, airway hyperreactivity, decreased lung capacity, fibrosis, airway inflammation and mucus production. A further symptom of asthma is exacerbations resulting from the original asthma attack which account for a significant morbidity from the disease. A KLK1 inhibitor can be used to ameliorate or prevent at least one symptom of asthma. A KLK1 inhibitor can also be administered in conjunction with another agent for treating asthma e.g. inhaled steroids, an oral steroid, a long acting beta-agonist, a leukotriene modifier, cromolyn sodium and nedocromil, theophylline and an anti-IgE antibody.

Allergic Rhinitis

Allergic rhinitis or “hay fever” involves an allergic reaction to pollen from grasses, trees, and weeds. When pollen is inhaled by an individual suffering from allergic rhinitis, antibody production and histamine release is triggered. Symptoms of allergic rhinitis include but are not limited to coughing, headache, itching of the eyes, mouth, throat, or nose, sneezing, nasal congestion, wheezing, sore throat, and watery eyes. The symptoms associated with hay fever vary significantly from person to person, and allergic rhinitis may be associated with other conditions such as asthma.

Chronic Obstructive Pulmonary Disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a disease involving inflammation of the airways. Emphysema, along with chronic bronchitis, is part of COPD. It is a serious lung disease and is progressive, usually occurring in elderly patients. COPD causes over-inflation of structures in the lungs known as alveoli or air sacs. The walls of the alveoli break down resulting in a decrease in the respiratory ability of the lungs. Patients with this disease may first experience shortness of breath and cough. The KLK1 inhibitor can be used to ameliorate at least one symptom of COPD.

Cough

Cough can be caused by inflammation of the upper respiratory tract (throat and windpipe) due to a viral infection. Viral infections include; the common cold, flu, laryngitis, and bronchitis. These viral infections can also spread to the lower respiratory tract (bronchi) to cause a cough. A cough is a symptom of many illnesses and conditions including: asthma, bronchitis, influenza and whooping cough (pertussis) and may also result as a side effect from use of certain drugs such as ACE inhibitors. Individuals who smoke often have a smoker's cough, a loud, hacking cough which often results in the expiration of phlegm. The KLK1 inhibitor can be used to ameliorate or prevent at least one symptom of cough.

Pancreatitis

Pancreatitis is an inflammation of the pancreas. There are two types:

Acute pancreatitis—the inflammation comes on quickly over a few hours, and will usually go away leaving no permanent damage, although it can be fatal if complications occur (5% of cases).

Chronic pancreatitis—this condition often starts with bouts of acute pancreatitis, and eventually becomes a permanent condition. The pancreas becomes constantly inflamed. The KLK1 inhibitor can be used to ameliorate or prevent at least one symptom of pancreatitis.

Rheumatoid Arthritis (RA)

This order is characterised by inflammation in the lining of the joints and/or other internal organs. It is typically chronic, but can include flare-ups. Symptoms include, inflammation of joints, swelling, difficulty moving, pain and fever. A KLK1 inhibitor may be used to ameliorate or prevent at least one symptom of rheumatoid arthritis. A KLK1 inhibitor can be administered with another agent for treating rheumatoid arthritis, such as NSAIDs and aspirin, analgesics and corticosteroids which help reduce joint pain, stiffness and swelling.

Osteoarthritis

Osteoarthritis is a degenerative joint disease. It is characterised by the breakdown of cartilage in the joint, thus causing bones to rub against each other, causing pain and loss of movement. A KLK1 inhibitor can be used to ameliorate or prevent at least one symptom of osteoarthritis. A KLK1 inhibitor can be administered with another agent for treating rheumatoid arthritis, such as a corticosteroid or an NSAID.

Angiogenesis-Associated and Neoplastic Disorders

In one embodiment, a KLK1 inhibitor may be administered to a subject to modulate angiogenesis or other processes associated with neoplasia and tumour growth.

For example a KLK1 inhibitor may be used to reduce angiogenesis (e.g. uncontrolled or unwanted angiogenesis) such as angiogenesis associated with vascular malformations and cardiovascular disorders (e.g. atherosclerosis, restenosis and arteriovenous malformations), chronic inflammatory diseases (e.g. diabetes mellitus, inflammatory bowel disease, psoriasis and rheumatoid arthritis), dermatological disorders (e.g. arterial ulcers, systemic vasculitis and scleroderma) or ocular disorders (e.g. blindness caused by neovascular disease, neovascular glaucoma, corneal neovascularization, trachoma, diabetic retinopathy and myopic degeneration).

In particular, a KLK1 inhibitor can be used to reduce angiogenesis associated with neoplasia, e.g., cancer and tumour growth, e.g., growth of a benign, malignant, or metastatic tumour.

Examples of cancerous disorders include, but are not limited to, solid tumours, soft tissue tumours and metastatic lesions. Examples include sarcomas, adenocarcinomas and carcinomas of various organ systems such as those affecting lung, breast, lymphoid, gastrointestinal (e.g. colon) and genitourinary tract (e.g. renal urothelial cells), pharynx, prostate, ovary as well as adenocarcinomas which include malignancies such as most colon cancers, rectal cancer, renal-cell carcinoma, liver cancer, non-small cell carcinoma of the lung, pharynx, cancer of the small intestine, cancer of the esophagus and others.

Exemplary solid tumours that can be treated include: fibrosarcoma, myxosarcoma, liposarcoma, chrondrosarcoma, osteogenic sarcoma, chordoma, lymphanangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumour, leiomyosaarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, heptoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, cervical cancer, testicular tumour, lung carcinoma, small cell lung carcinoma, non-small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemagioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma and retinoblastoma.

The KLK1 inhibitor can also be used to treat a carcinoma, e.g. a malignancy of epithelial or endocrine tissues including respiratory system carcinomas, gastrointestinal system carcinomas, genitourinary system carcinomas and melanoma. Exemplary carcinoma include adenocarcinoma, carcinomas of tissue of the cervix, lung, prostate, breast, head and neck, colon and ovary.

The KLK1 inhibitor can also be used to treat sarcomas, e.g. malignant tumours of mesenchchymal derivation.

The KLK1 inhibitor can be administered in combination with another agent for treating neoplastic and/or metastatic disorders. Examples of such other agents include:

(i) other antiangiogenic agents (e.g. linomide, angiostatin, razoxane);

(ii) cytostatic agents such as antiestrogens(e.g. tamoxifan, toremifene, raloxifene), progestogens(e.g. megestrol acetate), aromatase inhibitors (e.g. anastrozole, letrozole), antiprogestogens, antiandrogens(e.g. flutamide, nilutamide, bicalutamide), anti-invasion agents (e.g. metalloproteinase inhibitors such as marimastat and inhibitors of urokinase plasminogen activator receptor function).

(iii) antiproliferative/antineoplastic drugs and combinations thereof, as used in medical oncology, such as antimetabolites (e.g. fluoropyrimidines like 5-fluorouracil, purine and adenosine analogues, cytosine arabinoside); Intercalating antitumour antibiotics (e.g. anthracyclines like doxorubicin, daunomycin, epirubicin); platinum derivatives (e.g. cisplatin, carboplatin)alkylating agents (e.g. chlorambucil, cyclophosphamide); antmitotic agents (e.g. vinca alkaloids lsuch as vincristine and taxoids like TAXOL® (paclitaxel), TAXOTERE® (docetaxel, topoisomerase inhibitors (e.g. epipodophyllotoxins such as etoposide and teniposide) and proteasome inhibitors such as VELCADE® (bortezomib).

Accordingly, the present invention provides a compound of formula (I) for use in therapy.

The present invention also provides for the use of a compound of formula (I) in the manufacture of a medicament for the treatment or prevention of a disease or condition in which KLK1 activity is implicated. Diseases or conditions in which KLK1 activity is implicated include inflammation, respiratory disorders, disorders involving regulation of growth factors and neoplastic disorders. Specific examples of such diseases and conditions include those listed above.

The present invention also provides a compound of formula (I) for the treatment or prevention of a disease or condition in which KLK1 activity is implicated. Diseases or conditions in which KLK1 activity is implicated include inflammation, respiratory disorders, disorders involving regulation of growth factors and neoplastic disorders. Specific examples of such diseases and conditions include those listed above.

The present invention also provides a method of treatment of a disease or condition in which KLK1 activity is implicated comprising administration to a subject in need thereof a therapeutically effective amount of a compound of formula (I). Diseases or conditions in which KLK1 activity is implicated include inflammation, respiratory disorders, disorders involving regulation of growth factors and neoplastic disorders. Specific examples of such diseases and conditions include those listed above.

In one aspect, the disease or condition in which KLK1 activity is implicated is selected from an inflammatory or respiratory disorder or condition selected from asthma (allergic and non-allergic), chronic obstructive pulmonary disease (COPD), allergic rhinitis (hayfever), cough, exacerbations resulting from asthma and chronic obstructive pulmonary disease (COPD), multiple sclerosis, arthritis, rheumatoid arthritis, osteopathic arthritis, osteoarthritis, rhinitis, sinusitis, inflammatory bowel disease (such as Crohn's disease and ulcerative colitis), immune mediated diabetes, acute pancreatitis and interstitial cystitis, conjunctivitis, periodontal disease, chronic prostate inflammation, chronic recurrent parotitis, inflammatory skin disorders (e.g. psoriasis, eczema), and SIRS (systemic inflammatory response syndrome); smooth muscle spasm (e.g. asthma, angina), RDS (respiratory distress syndrome) , rhino-conjunctivitis, rhinorrhoea, urticaria or a neoplastic disorder.

In another aspect, the disease or condition in which KLK1 activity is implicated is a respiratory disorder selected from asthma (allergic and non-allergic), chronic obstructive pulmonary disease (COPD), allergic rhinitis (hayfever), cough, exacerbations resulting from asthma and chronic obstructive pulmonary disease (COPD),

In a further aspect, the disease or condition in which KLK1 activity is implicated is a respiratory disorder selected from asthma (allergic and non-allergic) and cough.

DEFINITIONS

The term “alkyl” includes saturated hydrocarbon residues including:

-   -   linear groups up to 10 atoms (C₁-C₁₀), or of up to 6 atoms         (C₁-C₆), or of up to 4 atoms (C₁-C₄). Examples of such alkyl         groups include, but are not limited, to C₁-methyl, C₂-ethyl,         C₃-propyl and C₄-n-butyl.     -   branched groups of between 3 and 10 atoms (C₃-C₁₀), or of up to         7 atoms (C₃-C₇), or of up to 4 atoms (C₃-C₄). Examples of such         alkyl groups include, but are not limited to, C₃-iso-propyl,         C₄-sec-butyl, C₄-iso-butyl, C₄-tert-butyl and C₅-neo-pentyl.

each optionally substituted as stated above.

The term “alkenyl” includes monounsaturated hydrocarbon residues including:

-   -   linear groups of between 2 and 6 atoms (C₂-C₆). Examples of such         alkenyl groups include, but are not limited to, C₂-vinyl,         C₃-1-propenyl, C₃-allyl, C₄-2-butenyl     -   branched groups of between 3 and 8 atoms (C₃-C₈). Examples of         such alkenyl groups include, but are not limited to,         C₄-2-methyl-2-propenyl and C₆-2,3-dimethyl-2-butenyl.

each optionally substituted as stated above.

The term “alkoxy” includes O-linked hydrocarbon residues including:

-   -   linear groups of between 1 and 6 atoms (C₁-C₆), or of between 1         and 4 atoms (C₁-C₄). Examples of such alkoxy groups include, but         are not limited to, C₁-methoxy, C₂-ethoxy, C₃-n-propoxy and         C₄-n-butoxy.     -   branched groups of between 3 and 6 atoms (C₃-C₆) or of between 3         and 4 atoms (C₃-C₄). Examples of such alkoxy groups include, but         are not limited to, C₃-iso-propoxy, and C₄-sec-butoxy and         tert-butoxy.

each optionally substituted as stated above.

Unless otherwise stated, halo is selected from Cl, F, Br and I.

Cycloalkyl is as defined above. Conveniently cycloalkyl groups may contain from 4 to 10 carbon atoms, or from 5 to 10 carbon atoms, or from 4 to 6 carbon atoms. Examples of suitable monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentene, cyclopenta-1,3-diene, cyclohexene and cyclohexa-1,4-diene (optionally substituted as stated above). Examples of suitable bicyclic cycloalkyl groups include decahydronaphthalene, octahydro-1H-indene (optionally substituted as stated above). Examples of suitable cycloalkyl groups, when fused with aryl, include indanyl and 1,2,3,4-tetrahydronaphthyl (optionally substituted as stated above).

Heterocycloalkyl is as defined above. Examples of suitable heterocycloalkyl groups include oxiranyl, aziridinyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, N-methylpiperidinyl, morpholinyl, N-methyl morpholinyl, thiomorpholinyl, thiomorpholinyl-1-oxide, thiomorpholinyl-1,1-dioxide, piperazinyl, N-methylpiperazinyl, azepinyl oxazepinyl, diazepinyl, and 1,2,3,4-tetrahydropyridinyl (optionally substituted as stated above).

Aryl is as defined above. Typically, aryl will be optionally substituted with 1, 2 or 3 substituents. Optional substituents are seleted from those stated above. Examples of suitable aryl groups include phenyl and naphthyl (each optionally substituted as stated above).

Heteroaryl is as defined above. Examples of suitable heteroaryl groups include thienyl, furanyl, pyrrolyl, pyrazolyl, imidazoyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzimidazolyl, benzotriazolyl, quinolinyl and isoquinolinyl (optionally substituted as stated above).

The term “C-linked”, such as in “C-linked heterocycloalkyl”, means that the heterocycloalkyl group is joined to the remainder of the molecule via a ring carbon atom.

The term “N-linked”, such as in “N-linked heterocycloalkyl”, means that the heterocycloalkyl group is joined to the remainder of the molecule via a ring nitrogen atom.

The term “O-linked”, such as in “O-linked hydrocarbon residue”, means that the hydrocarbon residue is joined to the remainder of the molecule via an oxygen atom.

In groups such as aryl(C₁-C₄)alkyl- and —SO₂(C₁-C₆)alkyl, “—” denotes the point of attachment of the group to the remainder of the molecule.

“Pharmaceutically acceptable salt” means a physiologically or toxicologically tolerable salt and includes, when appropriate, pharmaceutically acceptable base addition salts and pharmaceutically acceptable acid addition salts. For example (i) where a compound of the invention contains one or more acidic groups, for example carboxy groups, pharmaceutically acceptable base addition salts that can be formed include sodium, potassium, calcium, magnesium and ammonium salts, or salts with organic amines, such as, diethylamine, N-methyl-glucamine, diethanolamine or amino acids (e.g. lysine) and the like; (ii) where a compound of the invention contains a basic group, such as an amino group, pharmaceutically acceptable acid addition salts that can be formed include hydrochlorides, hydrobromides, sulfates, phosphates, acetates, citrates, lactates, tartrates, mesylates, succinates, oxalates, phosphates, esylates, tosylates, benzenesulfonates, naphthalenedisulphonates, maleates, fumarates, hippurates, xinafoates, p-acetamidobenzoates, dihydroxybenzoates, hydroxynaphthoates, succinates, ascorbates, oleates, bisulfates and the like.

Hemisalts of acids and bases can also be formed, for example, hemisulfate and hemicalcium salts.

For a review of suitable salts, see “Handbook of Pharmaceutical Salts: Properties, Selection and Use” by Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002).

“Prodrug” refers to a compound which is convertible in vivo by metabolic means (e.g. by hydrolysis, reduction or oxidation) to a compound of the invention. Suitable groups for forming pro-drugs are described in ‘The Practice of Medicinal Chemistry, 2^(nd) Ed. pp 561-585 (2003) and in F. J. Leinweber, Drug Metab. Res., 1987, 18, 379.

The compounds of the invention can exist in both unsolvated and solvated forms. The term ‘solvate’ is used herein to describe a molecular complex comprising the compound of the invention and a stoichiometric amount of one or more pharmaceutically acceptable solvent molecules, for example, ethanol. The term ‘hydrate’ is employed when the solvent is water.

Where compounds of the invention exist in one or more geometrical, optical, enantiomeric, diastereomeric and tautomeric forms, including but not limited to cis- and trans-forms, E- and Z-forms, R-, S- and meso-forms, keto-, and enol-forms. Unless otherwise stated a reference to a particular compound includes all such isomeric forms, including racemic and other mixtures thereof. Where appropriate such isomers can be separated from their mixtures by the application or adaptation of known methods (e.g. chromatographic techniques and recrystallisation techniques). Where appropriate such isomers can be prepared by the application or adaptation of known methods (e.g. asymmetric synthesis).

Typical configurations of the compounds of formula (I) include:

Other typical configurations of the compounds of formula (I) include:

In the context of the present invention, references herein to “treatment” include references to curative, palliative and prophylactic treatment.

General Methods

The compounds of formula (I) should be assessed for their biopharmaceutical properties, such as solubility and solution stability (across pH), permeability, etc., in order to select the most appropriate dosage form and route of administration for treatment of the proposed indication.

Compounds of the invention intended for pharmaceutical use may be administered as crystalline or amorphous products. They may be obtained, for example, as solid plugs, powders, or films by methods such as precipitation, crystallization, freeze drying, spray drying, evaporative drying, melt congealing and extrusion. Conventional drying processes including static/dynamic oven, infrared, microwave or radio frequency drying may be used to assist in the formation of the above crystalline and amorphous products.

They may be administered alone or in combination with one or more other compounds of the invention or in combination with one or more other drugs (or as any combination thereof). Generally, they will be administered as a formulation in association with one or more pharmaceutically acceptable excipients. The term ‘excipient’ is used herein to describe any ingredient other than the compound(s) of the invention which may impart either a functional (i.e., drug release rate controlling) and/or a non-functional (i.e., processing aid or diluent) characteristic to the formulations. The choice of excipient will to a large extent depend on factors such as the particular mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form.

Pharmaceutical compositions suitable for the delivery of compounds of the present invention and methods for their preparation will be readily apparent to those skilled in the art. Such compositions and methods for their preparation may be found, for example, in Remington's Pharmaceutical Sciences, 19th Edition (Mack Publishing Company, 1995).

Accordingly, the present invention provides a pharmaceutical composition comprising a compound of formula (I) and a pharmaceutically acceptable carrier, diluent or excipient.

The compounds of the invention may be administered orally. Oral administration may involve swallowing, so that the compound enters the gastrointestinal tract, and/or buccal, lingual, or sublingual administration by which the compound enters the blood stream directly from the mouth.

Formulations suitable for oral administration include solid plugs, solid microparticulates, semi-solid and liquid (including multiple phases or dispersed systems) such as tablets; soft or hard capsules containing multi- or nano-particulates, liquids, emulsions or powders; lozenges (including liquid-filled); chews; gels; fast dispersing dosage forms; films; ovules; sprays; and buccal/mucoadhesive patches.

Formulations suitable for oral administration may also be designed to deliver the compounds of formula (I) in an immediate release manner or in a rate-sustaining manner, wherein the release profile can be delayed, pulsed, controlled, sustained, or delayed and sustained or modified in such a manner which optimises the therapeutic efficacy of the said compounds. Means to deliver compounds in a rate-sustaining manner are known in the art and include slow release polymers that can be formulated with the said compounds to control their release.

Examples of rate-sustaining polymers include degradable and non-degradable polymers that can be used to release the said compounds by diffusion or a combination of diffusion and polymer erosion. Examples of rate-sustaining polymers include hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, sodium carboxymethyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, xanthum gum, polymethacrylates, polyethylene oxide and polyethylene glycol.

Liquid (including multiple phases and dispersed systems) formulations include emulsions, suspensions, solutions, syrups and elixirs. Such formulations may be presented as fillers in soft or hard capsules (made, for example, from gelatin or hydroxypropylmethylcellulose) and typically comprise a carrier, for example, water, ethanol, polyethylene glycol, propylene glycol, methylcellulose, or a suitable oil, and one or more emulsifying agents and/or suspending agents. Liquid formulations may also be prepared by the reconstitution of a solid, for example, from a sachet.

The compounds of the invention may also be used in fast-dissolving, fast-disintegrating dosage forms such as those described in Liang and Chen, Expert Opinion in Therapeutic Patents, 2001, 11(6), 981-986.

The formulation of tablets is discussed in Pharmaceutical Dosage Forms: Tablets, Vol. 1, by H. Lieberman and L. Lachman (Marcel Dekker, New York, 1980).

The compounds of the invention may also be administered directly into the blood stream, into subcutaneous tissue, into muscle, or into an internal organ. Suitable means for parenteral administration include intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscular, intrasynovial and subcutaneous. Suitable devices for parenteral administration include needle (including microneedle) injectors, needle-free injectors and infusion techniques.

Parenteral formulations are typically aqueous or oily solutions. Where the solution is aqueous, excipients such as sugars (including but restricted to glucose, manitol, sorbitol, etc.) salts, carbohydrates and buffering agents (preferably to a pH of from 3 to 9), but, for some applications, they may be more suitably formulated as a sterile non-aqueous solution or as a dried form to be used in conjunction with a suitable vehicle such as sterile, pyrogen-free water.

Parenteral formulations may include implants derived from degradable polymers such as polyesters (i.e., polylactic acid, polylactide, polylactide-co-glycolide, polycapro-lactone, polyhydroxybutyrate), polyorthoesters and polyanhydrides. These formulations may be administered via surgical incision into the subcutaneous tissue, muscular tissue or directly into specific organs.

The preparation of parenteral formulations under sterile conditions, for example, by lyophilisation, may readily be accomplished using standard pharmaceutical techniques well known to those skilled in the art.

The solubility of compounds of formula (I) used in the preparation of parenteral solutions may be increased by the use of appropriate formulation techniques, such as the incorporation of co-solvents and/or solubility-enhancing agents such as surfactants, micelle structures and cyclodextrins.

The compounds of the invention can also be administered intranasally or by inhalation, typically in the form of a dry powder (either alone, as a mixture, for example, in a dry blend with lactose, or as a mixed component particle, for example, mixed with phospholipids, such as phosphatidylcholine) from a dry powder inhaler, as an aerosol spray from a pressurised container, pump, spray, atomiser (preferably an atomiser using electrohydrodynamics to produce a fine mist), or nebuliser, with or without the use of a suitable propellant, such as 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoropropane, or as nasal drops. For intranasal use, the powder may comprise a bioadhesive agent, for example, chitosan or cyclodextrin.

The pressurised container, pump, spray, atomizer, or nebuliser contains a solution or suspension of the compound(s) of the invention comprising, for example, ethanol, aqueous ethanol, or a suitable alternative agent for dispersing, solubilising, or extending release of the active, a propellant(s) as solvent and an optional surfactant, such as sorbitan trioleate, oleic acid, or an oligolactic acid.

Prior to use in a dry powder or suspension formulation, the drug product is micronised to a size suitable for delivery by inhalation (typically less than 5 microns). This may be achieved by any appropriate comminuting method, such as spiral jet milling, fluid bed jet milling, supercritical fluid processing to form nanoparticles, high pressure homogenisation, or spray drying.

Capsules (made, for example, from gelatin or hydroxypropylmethylcellulose), blisters and cartridges for use in an inhaler or insufflator may be formulated to contain a powder mix of the compound of the invention, a suitable powder base such as lactose or starch and a performance modifier such as l-leucine, mannitol, or magnesium stearate. The lactose may be anhydrous or in the form of the monohydrate, preferably the latter. Other suitable excipients include dextran, glucose, maltose, sorbitol, xylitol, fructose, sucrose and trehalose.

Formulations for inhaled/intranasal administration may be formulated to be immediate and/or modified release using, for example, PGLA. Modified release formulations include delayed-, sustained-, pulsed-, controlled-, targeted and programmed release.

Inasmuch as it may desirable to administer a combination of active compounds, for example, for the purpose of treating a particular disease or condition, it is within the scope of the present invention that two or more pharmaceutical compositions, at least one of which contains a compound of formula (I), may conveniently be combined in the form of a kit suitable for coadministration of the compositions.

Thus the kit of the invention comprises two or more separate pharmaceutical compositions, at least one of which contains a compound of formula (I) in accordance with the invention, and means for separately retaining said compositions, such as a container, divided bottle, or divided foil packet. An example of such a kit is the familiar blister pack used for the packaging of tablets, capsules and the like.

The kit of the invention is particularly suitable for administering different dosage forms, for example, oral and parenteral, for administering the separate compositions at different dosage intervals, or for titrating the separate compositions against one another. To assist compliance, the kit typically comprises directions for administration and may be provided with a so-called memory aid.

In the present case, compounds of the present invention may be conveniently combined with an additional therapeutic agent or agents.

For example, as mentioned above, a KLK1 inhibitor can also be administered in conjunction with another agent for treating asthma e.g. inhaled steroids, an oral steroid, a long acting beta-agonist, a leukotriene modifier, cromolyn sodium and nedocromil, theophylline and an anti-IgE antibody.

If a combination of active agents is administered, then they may be administered simultaneously, separately or sequentially.

For administration to human patients, the total daily dose of the compounds of the invention is typically in the range 0.01 mg and 1000 mg, or between 0.1 mg and 250 mg, or between 1 mg and 50 mg depending, of course, on the mode of administration. The total daily dose may be administered in single or divided doses and may, at the physician's discretion, fall outside of the typical range given herein. These dosages are based on an average human subject having a weight of about 60 kg to 70 kg. The physician will readily be able to determine doses for subjects whose weight falls outside this range, such as infants and the elderly.

Synthetic Methods

The compounds of the present invention can be prepared according to the procedures of the following schemes and examples, using appropriate materials, and are further exemplified by the specific examples provided herein below. Moreover, by utilising the procedures described herein, one of ordinary skill in the art can readily prepare additional compounds that fall within the scope of the present invention claimed herein. The compounds illustrated in the examples are not, however, to be construed as forming the only genus that is considered as the invention. The examples further illustrate details for the preparation of the compounds of the present invention. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds.

The compounds of the invention may be isolated in the form of their pharmaceutically acceptable salts, such as those described previously herein above.

It may be necessary to protect reactive functional groups (e.g. hydroxy, amino, thio or carboxy) in intermediates used in the preparation of compounds of the invention to avoid their unwanted participation in a reaction leading to the formation of the compounds. Conventional protecting groups, for example those described by T. W. Greene and P. G. M. Wuts in “Protective groups in organic chemistry” John Wiley and Sons, 4^(th) Edition, 2006, may be used. For example, a common amino protecting group suitable for use herein is tert-butoxy carbonyl (Boc), which is readily removed by treatment with an acid such as trifluoroacetic acid or hydrogen chloride in an organic solvent such as dichloromethane. Alternatively the amino protecting group may be a benzyloxycarbonyl (Z) group which can be removed by hydrogenation with a palladium catalyst under a hydrogen atmosphere or 9-fluorenylmethyloxycarbonyl (Fmoc) group which can be removed by solutions of secondary organic amines such as diethylamine or piperidine in an organic solvents. Carboxyl groups are typically protected as esters such as methyl, ethyl, benzyl or tert-butyl which can all be removed by hydrolysis in the presence of bases such as lithium or sodium hydroxide. Benzyl protecting groups can also be removed by hydrogenation with a palladium catalyst under a hydrogen atmosphere whilst tert-butyl groups can also be removed by trifluoroacetic acid. Alternatively a trichloroethyl ester protecting group is removed with zinc in acetic acid. A common hydroxy protecting group suitable for use herein is a methyl ether, deprotection conditions comprise refluxing in 48% aqueous HBr for 1-24 hours, or by stirring with borane tribromide in dichloromethane for 1-24 hours. Alternatively where a hydroxy group is protected as a benzyl ether, deprotection conditions comprise hydrogenation with a palladium catalyst under a hydrogen atmosphere.

In the following schemes:

R¹-R⁷ and R¹¹ are as previously defined for the compounds of formula (I);

PG₁, PG₂ or PG₃ is a suitable protecting group;

R²⁰ is H, (C₁-C₁₀)alkyl, halogen, hydroxyl or (C₁-C₆)alkoxy;

R²¹ is H, (C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl, (C₃-C₁₀)cycloalkyl(C₁-C₄)alkyl-, aryl, heteroaryl, aryl(C₁-C₄)alkyl-, aryl(C₂-C₄)alkenyl-, or heteroaryl(C₁-C₄)alkyl-;

R²² is H, (C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl, (C₃-C₁₀)cycloalkyl(C₁-C₄)alkyl-, aryl, heteroaryl, aryl(C₁-C₄)alkyl-, aryl(C₂-C₄)alkenyl-, or heteroaryl(C₁-C₄)alkyl-; and

R²³ is H, (C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl, (C₃-C₁₀)cycloalkyl(C₁-C₄)alkyl-, aryl or aryl(C₁-C₄)alkyl-.

The compounds according to general formula I can be prepared using conventional synthetic methods. In a typical first step, 5-aminomethyl-pyridin-2-ylamine or substituted 5-aminomethyl-pyridin-2-ylamine (3) is prepared by reduction of the corresponding nitrile (2). This can be achieved either by direct reduction of the nitrile by hydrogenation in a suitable solvent such as methanol in the presence of a suitable catalyst such as palladium on charcoal in the presence of an acid such as hydrochloric acid or reduction with a suitable borohydride in the presence of a suitable transition metal such as cobalt or nickel chloride in a suitable solvent such as methanol at room temperature; or by trapping out of the tert-butoxycarbonyl (Boc) protected amine(4) (using, for example, the method as described in S. Caddick et al., Tetrahedron Lett., 2000, 41, 3513) which is then subsequently deprotected by standard means described previously to give the amine(3).

Alternatively amine (3) can be prepared from the corresponding acid (5) via a primary amide (6). Typically, acid (5) is treated with ammonia in the presence of a suitable coupling reagent in a suitable solvent such as dichloromethane and DMF at room temperature. The resulting amide (6) is then reduced with a reducing agent such as lithium aluminium hydride in a suitable solvent such as tetrahydrofuran at room temperature to yield amine (3).

In a typical second step, the amine (3) is coupled using standard peptide coupling conditions to an alpha amino acid (7) suitably amino-protected with a standard protecting group such as tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Z) or 9-fluorenylmethyloxycarbonyl (Fmoc). The use of such groups is well known in the art. Where R²¹ has a reactive functional group such as an amine or a carboxylic acid, this group will also be protected. Standard peptide coupling methods include the reaction of acids with amines in the presence of hydroxybenzotriazole and carbodiimide such as water soluble carbodiimide, or 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium hexafluorophosphate or benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphoium hexaffluorophosphate or bromo-trispyrolidino-phosphoium hexafluorophosphate in the presence of organic bases such as triethylamine, diisopropylethylamine or N-methylmorpholine.

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The protecting group of (8) is removed using standard methods described previously to yield the amine (9).

The amine (9) is coupled using the standard peptide coupling conditions described previously to an alpha amino acid (10) suitably amino-protected with a suitable protecting group such as tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Z) or 9-fluorenylmethyloxycarbonyl (Fmoc). Where R¹ or R² has a reactive functional group such as an amine or a carboxylic acid, this group will also be protected. The protecting group of the resulting protected dipeptide derivative (11) is removed using the standard methods described previously to give the amine (12).

The amine (12) is further derivatised by reductive alkylation with a suitable aldehyde or ketone to yield the alkylated amine (13). Typically, amine (12) is allowed to react with the aldehyde or ketone in the presence of a suitable reducing agent such as sodium cyanoborohydride or sodium acetoxyborohydride in a suitable solvent such as methanol, at room temperature.

Compound 15 can also be prepared by coupling the alkylated alpha amino acid (14) with the amine (9) using standard peptide coupling conditions described previously.

Alkylated alpha amino acids (17) can be prepared by the reductive alkylation of the parent alpha amino acid in which the carboxyl group is unprotected (16) or in which it is protected as an ester with a standard protecting group such as a methyl, tert-butyl or trichloroethyl ester (18), following alkylation this protecting group is removed using standard methods described previously. Typical conditions for carrying out the reductive alkylation are described above.

Alternatively the alpha amino acid (14) may be prepared from the corresponding bromoacetic acid derivative, suitably carboxyl-protected with a standard protecting group, such as a methyl, tert-butyl, trichloroethyl ester (19) by reaction with the required amine followed by the deprotection using standard methods. Typically, bromoacetic acid derivative (19) is allowed to react with the amine in the presence of a base such as diisopropylethylamine or potassium or sodium carbonate in a suitable solvent such as acetonitrile or tetrahydrofuran at room temperature.

Compound (11) can also be synthesised from the dipeptide (22) suitably amino-protected with a standard protecting group such as tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Z) or 9-fluorenylmethyloxycarbonyl (Fmoc). Such a dipeptide can be prepared from two alpha amino acids one of which is amino-protected with a standard protecting group such as tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Z) or 9-fluorenylmethyloxycarbonyl (Fmoc) whilst the other is carboxyl-protected with a standard protecting group such as an ester such as a methyl, tert-butyl, trichloroethyl ester. The carboxyl protecting group of (21) is removed by standard methods described previously following the coupling reaction. The amide bond forming reactions may be carried out using the standard peptide coupling conditions described above.

The amine 12 can be further derivatised by reaction with a sulphonyl chloride in the presence of a base such as triethylamine or diisopropylamine to yield the sulphonamide (23).

The present invention also encompasses intermediate compounds that have utility in the synthesis of the compounds of formula (I). Accordingly, one aspect of the present invention provides an intermediate compound selected from the group including:

{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-carbamic acid tert-butyl ester;

(S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-naphthalen-1-yl-propionamide ditrifluoroacetate;

((R)-1-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethylcarbamoyl}-2-methyl-butyl)-carbamic acid tert-butyl ester;

[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-carbamic acid tert-butyl ester;

(S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(decahydro-naphthalen-1-yl)-propionamide dihydrochloride;

{(R)-1-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester;

{(S)-1-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester;

(S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide dihydrochloride;

{(R)-1-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethylcarbamoyl]-2-methyl-butyl}-methyl-carbamic acid tert-butyl ester;

(R)-2-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester;

[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester;

(S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-propionamide dihydrochloride;

{(S)-1-[(6-Amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-carbamic acid tert-butyl ester;

(S)-2-Amino-N-(6-amino-2-methyl-pyridin-3-ylmethyl)-3-naphthalen-1-yl-propionamide dihydrochloride;

{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-carbamic acid tert-butyl ester;

(R)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3,3-dicyclohexyl-propionamide ditrifluoroacetate; and

((S)-1-{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethylcarbamoyl}-2-methyl-butyl)-carbamic acid tert-butyl ester.

In one aspect, the present invention provides a process for the preparation of a compound of formula (I),

comprising the reaction of a compound of formula (IV):

with a compound of formula (V):

under standard peptide coupling conditions; wherein R¹-R¹² are as previously defined for the compounds of formula (I).

Standard peptide coupling conditions include the reaction of acids with amines in the presence of hydroxybenzotriazole and carbodiimide such as water soluble carbodiimide, or 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium hexafluorophosphate or benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphoium hex affluorophosphate or bromo-trispyrolidino-phophoium hexafluorophosphate in the presence of organic bases such as triethylamine, diisopropylethylamine or N-methylmorpholine. These reactions are typically carried out in solvents such as dichloromethane and dimethylformamide.

EXAMPLES

The invention is illustrated by the following non-limiting examples in which the following abbreviations and definitions are used:

DMF N,N-Dimethylformamide EtOAc Ethyl Acetate hrs Hours HBTU 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate HOBt Hydroxybenzotriazole Ile Isoleucine LCMS Liquid chromatography mass spectrometry Me Methyl MeCN Acetonitrile MeOH Methanol Min Minutes MS Mass spectrum Nal Napthylalanine NMR Nuclear magnetic resonance spectrum - NMR spectra were recorded at a frequency of 270 or 400 MHz unless otherwise indicated Pet. Ether Petroleum ether fraction boiling at 60-80° C. Phe Phenylalanine Pro Proline PyBOP ® Benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphoium hexafluorophosphate THF Tetrahydrofuran TFA Trifluoroacetic acid

All reactions were carried out under an atmosphere of nitrogen unless specified otherwise.

¹H NMR spectra were recorded on a Jeol EX 270 (270 MHz) or Brucker Avance III (400 MHz) spectrometer with reference to deuterium solvent and at room temperature. Molecular ions were obtained using LCMS which was carried out using a Chromolith Speedrod RP-18e column, 50×4.6 mm, with a linear gradient 10% to 90% 0.1% HCO₂H/MeCN into 0.1% HCO₂H/H₂O over 11 min, flow rate 1.5 mL/min. Data was collected using a Thermofinnigan Surveyor MSQ mass spectrometer with electospray ionisation in conjunction with a Thermofinnigan Surveyor LC system.

Chemical names were generated using the Autonom software provided as part of the ISIS draw package from MDL Information Systems.

Where products were purified by flash chromatography, ‘silica’ refers to silica gel for chromatography, 0.035 to 0.070 mm (220 to 440 mesh) (e.g. Merck silica gel 60), and an applied pressure of nitrogen up to 10 p.s.i accelerated column elution. Reverse phase preparative HPLC purifications were carried out using a Waters 2525 binary gradient pumping system at flow rates of typically 20 ml/min using a Waters 2996 photodiode array detector.

All solvents and commercial reagents were used as received.

Example 1 (R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide

A. (6-Amino-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

2-Amino-5-cyanopyridine (2.0 g, 16.8 mmol) was dissolved in methanol (100 ml). This solution was cooled to 0° C. Nickel (II) chloride hexahydrate (0.4 g, 1.67 mmol) and di-tertbutyl dicarbonate (7.33 g, 33.6 mmol) were added followed by sodium borohydride (4.49 g, 117 mmol) portionwise. The reaction mixture was stirred at 0° C. to room temp for 18 hrs. The MeOH was removed by evaporation. The residue was dissolved in EtOAc (100 ml), washed with sat NaHCO₃ (1×50 mls), water (1×50 mls), brine (1×50 mls), dried (Na₂SO4) and evaporated in vacuo to give a brown oil. Purified by flash chromatography, eluant 3% MeOH, 97% CHCl₃ to give an orange oil identified as the title compound.

Yield=2.74 g, 12.25 mmol, 73%

[M+H]⁺=224.1

B. 5-Aminomethyl-pyridin-2-ylamine dihydrochloride

(6-Amino-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (2.74 g, 12.25 mmol) was dissolved in 4M HCl/dioxan (50 mls). After one hour at room temp the solvent was removed in vacuo to give a pale yellow solid identified as the title compound.

Yield=2.3 g, 12.1 mmol, 99%

[M+H]⁺=124.1

C. {(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-carbamic acid tert-butyl ester

Boc-1Nal-OH (1.0 g, 2.66 mmol) was dissolved in CH₂Cl₂ (30 mls). Triethylamine (0.805 g, 7.96 mmol) and HBTU (1.21 g, 3.18 mmol) was added followed by 5-aminomethyl-pyridin-2-ylamine dihydrochloride (0.52 g, 2.66 mmol). After 3 hours at room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 3% MeOH, 97% CHCl₃, fractions combined and evaporated in vacuo to give a colourless oil identified as the title compound.

Yield=1.18 g, 2.15 mmol, 81%

[M+H]⁺=421.27

D. (S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-naphthalen-1-yl-propionamide ditrifluoroacetate

{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-carbamic acid tert-butyl ester (1.18 g, 2.81 mmol) was treated with trifluoroacetic acid (30 mls). After 1 hour at room temperature the solvent was removed in vacuo giving a pale brown solid identified as the title compound.

Yield=1.53 g, 2.8 mmol, 99%

[M+H]⁺=321.1

E. ((R)-1-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethylcarbamoyl}-2-methyl-butyl)-carbamic acid tert-butyl ester

(S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-naphthalen-1-yl-propionamide ditrifluoroacetate (120 mg, 0.22 mmol) was dissolved in CH₂Cl₂ (20 mls) and DMF (2 mls). This solution was cooled to 0° C. Boc-DIle-OH (65 mg, 0.28 mmol) was added followed by HOBt (65 mg, 0.48 mmol) and water soluble carbodiimide (62 mg, 0.31 mmol). After 15 mins triethylamine (49 mg, 0.49 mmol) was added. After 18 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 3% MeOH, 97% CHCl₃, fractions combined and evaporated in vacuo to give a colourless oil identified as the title compound.

Yield=98 mg, 0.18 mmol, 81%

[M+H]⁺=534.3

F. (R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide ditrifluoroacetate

((R)-1-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethylcarbamoyl}-2-methyl-butyl)-carbamic acid tert-butyl ester (89 mg, 0.16 mmol) was treated with trifluoroacetic acid (30 mls). After 1 hour at room temperature the solvent was removed in vacuo and the residue purified by Prep HPLC. (19×250 mm Sunfire C-18 Column) 10 to 90% 0.1% TFA/MeCN into 0.1%TFA/H₂O over 35 min at 20 ml/min. Fractions combined and freeze dried to give a white solid identified as the title compound.

Yield 65 mg, 0.125 mmol, 78%

[M+H]⁺=434.2

¹H NMR: (270 MHz) (CD₃OD) 0.75 (6H, t, J=6.9 Hz), 1.1-1.2 (1H, m), 1.7-1.8 (1H, m), 3.31-3.37 (3H, m), 3.66-3.72 (3H, m), 4.14-4.26 (2H, m), 4.82-4.90 (5H, m), 6.87 (1H, d, J=8.4 Hz), 7.39 (2H, s), 7.49-7.61 (3H, m), 7.76-7.79 (1H, m), 7.86-7.89 (1H, m), 8.16-8.19 (1H, m), 8.65 (1H,s, br).

Example 2 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide

A. (S)-2-tert-Butoxycarbonylamino-3-(decahydro-naphthalen-1-yl)-propionic acid

Boc-1-napthylalanine (6.0 g, 19.053 mmol) was dissolved in methanol (150 mls). This solution was hydrogenated over 5% Rh on carbon (100 mg) at 70 psi and room temperature. After 2 days the catalyst was filtered off through celite and the residue washed with MeOH (100 mls). The combined filtrates were evaporated in vacuo to give a pale yellow oil identified as the title compound.

Yield=6.15 g, 19.05 mmol, 100%

B. [(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-carbamic acid tert-butyl ester

(S)-2-tert-Butoxycarbonylamino-3-(decahydro-naphthalen-1-yl)-propionic acid (800 mg, 2.43 mmol) was dissolved in CH₂Cl₂ (60 mls) and DMF (62 mls). This solution was cooled to 0° C. 5-Aminomethyl-pyridin-2-ylamine dihydrochloride (760 mg, 3.86 mmol) was added followed by HOBt (680 mg, 5.0 mmol) and water soluble carbodiimide (590 mg, 2.95 mmol). After 15 mins triethylamine (115 mg, 1.13 mmol) was added. After 18 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 3% MeOH, 97% CHCl₃, fractions combined and evaporated in vacuo to give a yellow oil identified as the title compound.

Yield=310 mg, 0.72 mmol, 30%

C. (S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(decahydro-naphthalen-1-yl)-propionamide dihydrochloride

[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-carbamic acid tert-butyl ester (310 mg, 0.72 mmol) was treated with 4M HCl in dioxan (30 mls). After 1 hour at room temperature the solvent was removed in vacuo giving a pale brown solid identified as the title compound.

Yield=290 mg, 0.72 mmol, 100%

D. {(R)-1-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester

(S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(decahydro-naphthalen-1-yl)-propionamide dihydrochloride (82 mg, 0.22 mmol) was dissolved in CH₂Cl₂ (20 mls) and DMF (2 mls). This solution was cooled to 0° C. Boc-DIle-OH (62 mg, 0.27 mmol) was added followed by HOBt (61 mg, 0.45 mmol) and water soluble carbodiimide (54 mg, 0.27 mmol). After 15 mins triethylamine (49 mg, 0.49 mmol) was added. After 18 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 3% MeOH, 97% CHCl₃, fractions combined and evaporated in vacuo to give a yellow oil identified as the title compound.

Yield=55 mg, 0.10 mmol, 46%

E. (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide ditrifluoroacetate

{(R)-1-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester (45 mg, 0.083 mmol) was treated with trifluoroacetic acid (30 mls). After 1 hour at room temperature the solvent was removed in vacuo and the residue purified by Prep HPLC (19×250 mm Sunfire C-18 Column). 10 to 90% 0.1% TFA/MeCN into 0.1% TFA/H₂O over 35 min at 20 ml/min. Fractions combined and freeze dried to give a white solid identified as the title compound.

Yield 27 mg, 0.04 mmol, 48%

[M+H]⁺=444.3

¹H NMR: (270 MHz) (CD₃OD) 0.96-1.05 (6H, m), 1.25-1.78 (28H, m), 3.76-3.86 (1H, m), 4.26-4.28 (3H, m), 6.97 (1H, d, J=9Hz), 7.74 (1H, s), 7.80-7.90 (1H, m)

Example 3 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide

A. 5-Aminomethyl-pyridin-2-ylamine dihydrochloride

6-Amino-3-pyridinecarbonitrile (12.5 g, 104 mmol) was dissolved (250 mls), 6M HCl (35 mls, 210 mmol) was added. 10% Pd/C (2.5 g) was added. The reaction mixture was shaken at 10 psi for 18 hours after which time the catalyst was filtered off through celite and the residue washed with methanol (200 mls) and water (20 mls). The combined filtrates were evaporated in vacuo to give a white solid. Recrystallised from MeOH/diethyl ether to give a white solid identified as the title compound

Yield=15.52 g, 79.2 mmol, 75%

[M+H]⁺=124.17

B. {(S)-1-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester

Boc-3,4-dichloro-Phe-OH (1.71 g, 5.1 mmol) was dissolved in CH₂Cl₂ (30 mls) and DMF (3 mls). This solution was cooled to 0° C. 5-Aminomethyl-pyridin-2-ylamine dihydrochloride (1.0 g, 5.1 mmol) was added followed by HOBt (827 mg, 6.1 mmol) and water soluble carbodiimide (978 mg, 5.1 mmol). After 15 mins diisopropylethylamine (1.98 g, 15.3 mmol) was added. After 5 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 5% MeOH, 95% CHCl₃, fractions combined and evaporated in vacuo to give a yellow oil identified as the title compound.

Yield=1.44 g, 3.28 mmol, 64%

[M+H]⁺=439.20

C. (S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide dihydrochloride

{(S)-1-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester (1.44 g, 3.28 mmol) was treated with 4M HCl in dioxan (50 mls). After 1 hour at room temperature the solvent was removed in vacuo giving a pale brown solid identified as the title compound.

Yield=1.3 g, 3.15 mmol, 96%

[M+H]⁺=339.0, 340.9

D. {(R)-1-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethylcarbamoyl]-2-methyl-butyl}-methyl-carbamic acid tert-butyl ester

(S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide dihydrochloride (1.3 g, 3.3 mmol) was dissolved in CH₂Cl₂ (20 mls) and DMF (2 mls). This solution was cooled to 0° C. Boc-N-Me-DIle-OH (811 mg, 3.3 mmol) was added followed by HOBt (536 mg, 3.9 mmol) and water soluble carbodiimide (633 mg, 3.3 mmol). After 15 mins diisopropylethylamine (1.3 g, 9.9 mmol) was added. After 5 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 4% MeOH, 96% CHCl₃, fractions combined and evaporated in vacuo to give a yellow oil identified as the title compound.

Yield=983 mg, 1.74 mmol, 53%

[M+H]⁺=566.25, 568.26

E. (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide dihydrochloride

{(R)-1-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethylcarbamoyl]-2-methyl-butyl}-methyl-carbamic acid tert-butyl ester (983 mg, 1.74 mmol) was treated with 4M HCl in dioxan (30 mls). After 1 hour at room temperature the solvent was removed in vacuo, azetroped from toluene and the residue freeze dried from water to give a white solid identified as the title compound.

Yield 880 mg, 1.63 mmol, 94%

[M+H]⁺=466.01

¹H NMR: (270 MHz) (CD₃OD) 0.75-0.90 (7H, m), 1.20-1.40 (1H, m), 1.70-1.90 (1H, m), 2.62 (3H, s), 2.85-3.00 (1H, m), 3.15-3.25 (1H, m), 3.30-3.35 (2H, m), 3.65-3.75 (1H, m), 4.20-4.40 (2H, m), 4.60-4.70 (1H, m), 4.90-5.10 (2H, m), 6.90-7.10 (1H, m), 7.20-7.30 (1H, m), 7.40-7.50 (2H, m), 7.70-7.90 (2H, m), 8.75-8.85 (1H, m).

Example 4 (R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide

A. (R)-2-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Boc-DPro-OH (238 mg, 1.11 mmol) was dissolved in CH₂Cl₂ (30 mls). Triethylamine (323 mg, 3.32 mmol) and HBTU (419 mg, 1.11 mmol) was added followed by (S)-2-amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide dihydrochloride (435 mg, 1.11 mmol). After 3 hours at room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 5% MeOH, 99% CHCl₃, fractions combined and evaporated in vacuo to give a yellow oil identified as the title compound.

Yield=263 mg, 0.49 mmol, 44%

[M+H]⁺=536.2

B. (R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide dihydrochloride

(R)-2-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (263 mg, 0.49 mmol) was treated with 4M HCl in dioxan (30 mls). After 1 hour at room temperature the solvent was removed in vacuo, azetroped from toluene and the residue freeze dried from water to give a white solid identified as the title compound.

Yield 232 mg, 0.46 mmol, 93%

[M+H]⁺=436.0, 438.1

¹H NMR: (270 MHz) (CD₃OD) 1.60-2.10 (3H, m), 2.20-2.40 (1H, m), 2.80-3.50 (5H, m), 4.10-4.35 (3H, m), 4.55-4.85 (1H, m), 4.80-5.10 (3H, m), 6.90-7.00 (1H, m), 7.10-7.25 (1H, m), 7.30-7.50 (2H, m), 7.70-7.90 (2H, m), 8.70-8.90 (1H, m)

Example 5 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide

A. (R)-1-Methyl-pyrrolidine-2-carboxylic acid (N-Me-DPro-OH)

H-DPro-OH (10.0 g, 86.9 mmol) was dissolved in methanol (200 mls), formaldehyde (37% by weight solution, 7 mls) was added followed by 10% Pd/C (5 g). The reaction mixture was shaken at 15 psi for 18 hours. After this time the catalyst was filtered off through Celite and the residue washed with MeOH (100 mls). The combined filtrates were evaporated in vacuo to give a white solid which was recystallised from MeOH/diethyl ether to give a white crystalline solid identified as the title compound

Yield=10.72 g, 83 mmol, 96%

[M+H]⁺=130.17

B. [(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester

Boc-3,4-difluoro-Phe-OH (5.0 g, 16.6 mmol) was dissolved in CH₂Cl₂(100 mls) and DMF (10 mls). This solution was cooled to 0° C. 5-Aminomethyl-pyridin-2-ylamine dihydrochloride (3.58 g, 18.2 mmol) was added followed by HOBt (2.69 g, 19.9 mmol) and water soluble carbodiimide (3.18 g, 16.6 mmol). After 15 mins diisopropylethylamine (6.44 g, 49.8 mmol) was added. After 5 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (150 mls), this solution was washed with sat. NaHCO₃ (1×50 mls), water (1×50 mls), brine (1×50 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 5% MeOH, 95% CHCl₃, fractions combined and evaporated in vacuo to give a yellow oil identified as the title compound.

Yield=5.79 g, 14.2 mmol, 88%

[M+H]⁺=407.16

C. (S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-propionamide dihydrochloride

[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester (5.79 g, 14.2 mmol) was treated with 4M HCl in dioxan (50 mls). After 1 hour at room temperature the solvent was removed in vacuo giving a pale brown solid identified as the title compound.

Yield=5.4 g, 14.2 mmol, 100%

[M+H]⁺=307.05

D. (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide dihydrochloride

((S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-propionamide dihydrochloride (5.55 g, 14.6 mmol) was dissolved in CH₂Cl₂ (100 mls) and DMF (10 mls). This solution was cooled to 0° C. N-Me-DPro-OH (1.89 g, 14.63 mmol) was added followed by HOBt (2.37 g, 17.5 mmol) and water soluble carbodiimide (3.93 g, 20.5 mmol). After 15 mins diisopropylethylamine (5.67 g, 43.9 mmol) was added. After 5 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (150 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×50 mls), brine (1×50 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 7% MeOH, 93% CHCl₃, fractions combined and evaporated in vacuo to give a white solid. This solid was dissolved in 4M HCl in dioxan (100 mls), after 30 mins the solvent was removed in vacuo and the residue freeze dried from water and MeCN to yield a white solid identified as the title compound.

Yield=2.9 g, 5.91 mmol, 40%

[M+H]⁺=418.06 ¹H NMR: (270 MHz) (CD₃OD) 1.60-2.25 (3H, m), 2.40-2.60 (1H, m), 2.90 (3H, s), 3.10-3.20 (2H, m), 3.25-3.35 (2H, m), 3.60-3.75 (1H, m), 4.10-4.35 (3H, m), 4.60-4.80 (1H, m), 4.90-5.10 (2H, m), 6.90-7.30 (4H, m), 7.70-7.90 (2H, m), 8.75-8.90 (1H, m)

Example 6 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide

A. (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid

H-DPro-OH (5.0 g, 43.3 mmol) was dissolved in methanol (200 mls), acetone (3.78 g, 58.1 mmol) was added followed by 10% Pd/C (2.5 g). The reaction mixture was shaken at 15 psi for 18 hours. After this time the catalyst was filtered off through celite and the residue washed with MeOH (100 mls). The combined filtrates were evaporated in vacuo to give a white solid which was recystallised from MeOH/diethyl ether to give a white crystalline solid identified as the title compound

Yield=5.747 g, 33.4 mmol, 77%

[M+H]⁺=158.14

B. (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide ditrifluoroacetate

(R)-1-Isopropyl-pyrrolidine-2-carboxylic acid (187 mg, 1.19 mmol) was dissolved in CH₂Cl₂(30 mls). Triethylamine (601 mg, 5.95 mmol) and HBTU (451 mg, 1.19 mmol) was added followed by ((S)-2-amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-propionamide dihydrochloride (451 mg, 1.19 mmol). After 3 hours at room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by Prep HPLC (19×250 mm Sunfire C-18 Column). 10 to 90% 0.1% TFA/MeCN into 0.1% TFA/H₂O over 35 min at 20 ml/min. Fractions combined and freeze dried to give a white solid identified as the title compound.

Yield=63 mg, 0.094 mmol, 8%

[M+H]⁺=446.13

¹H NMR: (270 MHz) (CD₃OD) 1.15-1.21 (6H, m) 1.70 (1H, br, s) 1.95 (1H, br, s) 2.31 (1H, br, s) 2.80-3.07 (3H, m) 3.42-3.52 (2H, m) 4.12-4.18 (3H, m) 4.50-4.56 (1H, m) 4.87 (5H, br, s) 6.85-7.08 (4H, m) 7.64-7.70 (2H, m)

Example 7 (R)-1-Benzyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide

A. (R)-1-Benzyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide ditrifluoroacetate

(R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide dihydrochloride (50 mg, 0.075 mmol) was taken up in methanol/acetic acid (9:1, 10 mls). Benzaldehyde (7.9 mg, 0.075 mmol) was added and the solution stirred at room temp for 1 hour. Sodium cyanoborohydride (9.45 mg, 0.15 mmol) was added. After 18 hours at room temperature the solvent was removed in vacuo and the residue dissolved in CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by Prep HPLC (19×250 mm Sunfire C-18 Column). 10 to 90% 0.1% TFA/MeCN into 0.1% TFA/H₂O over 35 min at 20 ml/min. Fractions combined and freeze dried to give a white solid identified as the title compound.

Yield=15 mg, 0.02 mmol, 26%

[M+H]⁺=526.06

¹H NMR: (270 MHz) (CD₃OD) 1.60-2.60 (4H, m), 2.80-2.90 (1H, m), 3.00-3.10 (1H, m), 3.20-3.40 (3H, m), 3.45-3.60 (1H, m), 4.05-4.40 (5H, m), 4.50-4.60 (1H, m), 4.75-4.95 (1H, m), 6.90-7.00 (1H, m), 7.05-7.10 (1H, m), 7.30-7.50 (7H, m), 7.65-7.80 (2H, m), 8.60-8.70 (1H, m)

Example 8 (R)-2-(Methanesulfonyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide

A. (R)-2-(Methanesulfonyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide trifluoroacetate

(R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide ditrifluoroacetate (80 mg, 0.15 mmol) was dissolved in CH₂Cl₂ (30 mls). This solution was cooled to 0° C. triethylamine (30 mg, 0.30 mmol) was added followed by methanesulphonyl chloride (17 mg, 0.15 mmol). After 1 hr at 0° C. the reaction mixture was diluted with CHCl₃ (150 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×50 mls), brine (1×50 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by Prep HPLC (19×250 mm Sunfire C-18 Column). 10 to 90% 0.1% TFA/MeCN into 0.1% TFA/H₂O over 35 min at 20 ml/min. Fractions combined and freeze dried to give a white solid identified as the title compound.

Yield 10 mg, 0.015 mmol, 10%

[M+H]⁺=544.01

¹H NMR: (270 MHz) (CD₃OD) 0.54 (3H, d, J=6.70 Hz), 0.75-1.10 (5H, m), 1.45-1.60 (1H, m), 1.70-1.90 (1H, m), 2.86 (3H, s), 2.87 (3H, s), 3.10-3.30 (3H, m), 3.84 (1H, d, J=10.88 Hz), 4.10-4.40 (2H, m), 4.50-4.70 (1H, m), 6.95 (1H, d, J=9.15 Hz), 7.15-7.30 (1H, m), 7.35-7.50 (2H, m), 7.70-7.80 (2H, m), 8.35-8.50 (1H, m), 8.60-8.70 (1H, m)

Example 9 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl]-amide

A. 5-Aminomethyl-6-methyl-pyridin-2-ylamine

6-Amino-2-methylnicotinonitrile (2.0 g, 15.03 mmol) was dissolved in methanol (150 ml). This solution was cooled to 0° C. Cobalt chloride hexahydrate (8.0 g, 33.7 mmol) was added followed by sodium borohydride (6.4 g, 168 mmol) portionwise. The reaction mixture was stirred at 0° C. to room temp for 3 hrs and 3M HCl (100 ml) was added. The MeOH was removed by evaporation. The aqueous residue was washed with EtOAc (100 ml), basified with ammonium hydroxide and extracted with CHCl₃ (3×150 ml). The combined organic extracts were washed with water (1×50 mls), brine (1×50 mls), dried (Na₂SO₄) and evaporated in vacuo to give a brown oil identified as the title compound.

Yield=820 mg, 5.99 mmol, 40%

B {(S)-1-[(6-Amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-carbamic acid tert-butyl ester

Boc-1Nal-OH (1.5 g, 4.76 mmol) was dissolved in CH₂Cl₂ (30 mls). Triethylamine (0.95 g, 9.5 mmol) and HBTU (1.98 g, 5.23 mmol) was added followed by 5-aminomethyl-pyridin-2-ylamine dihydrochloride (0.83 g, 4.76 mmol). After 3 hours at room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 3% MeOH, 97% CHCl₃, fractions combined and evaporated in vacuo to give a colourless oil identified as the title compound.

Yield=1.5 g, 3.44 mmol, 72%

[M+H]⁺=435.29

C. (S)-2-Amino-N-(6-amino-2-methyl-pyridin-3-ylmethyl)-3-naphthalen-1-yl-propionamide dihydrochloride

{(S)-1-[(6-Amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-carbamic acid tert-butyl ester (1.5 g, 3.44 mmol) was treated with 4M HCl in dioxan (30 mls). After 1 hour at room temperature the solvent was removed in vacuo giving a pale brown solid identified as the title compound.

Yield=969 mg, 2.38 mmol, 69%

[M+H]⁺=334.1

D. (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide ditrifluoroacetate

N-Me-DPro-OH (66 mg, 0.51 mmol) was dissolved in CH₂Cl₂ (30 mls). Triethylamine (110 mg, 1.1 mmol) and HBTU (211 mg, 0.56 mmol) was added followed by (S)-2-amino-N-(6-amino-2-methyl-pyridin-3-ylmethyl)-3-naphthalen-1-yl-propionamide dihydrochloride (200 mg, 0.51 mmol). After 3 hours at room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by Prep HPLC (19×250 mm Sunfire C-18 Column). 10 to 90% 0.1% TFA/MeCN into 0.1% TFA/H₂O over 35 min at 20 ml/min. Fractions combined and freeze dried to give a white solid identified as the title compound.

Yield=118 mg, 0.27 mmol, 54%

[M+H]⁺=446.02

¹H NMR: (400 MHz) (DMSO-d⁶) 1.8-2.0 (1H, m), 2.2-2.3 (3H, m), 2.5-2.6 (2H, m), 2.7-2.8 (3H, m), 3.0-3.3 (1H, m), 3.3-3.8 (6H, m), 3.7-4.3 (3H, m), 4.7-4.8 (1H, m), 6.7-6.9 (1H, d, J=8 Hz), 7.1-7.2 (1H, m), (7.3-7.4 (2H, m), 7.7-8.0 (3H, m), 8.2-8.3 (1H, m), 8.7 (1H, m), 9.1-9.3 (1H, m), 9.4-9.6 (1H, m)

Example 10 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-(2-diethylamino-acetylamino)-3-(3,4-difluoro-phenyl)-propionamide

A. Diethylamino-acetic acid tert-butyl ester

Diethylamine (177 mg, 2.42 mmol) and potassium carbonate (401 mg, 2.90 mmol) were added to a solution of tert-butylbromoacetate (470 mg, 2.42 mmol) in acetonitrile (10 mls). After stirring at room temperature for 18 hours the solvent was removed in vacuo and the residue taken up in ethyl acetate (50 mls). This solution was washed with water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo giving a brown oil identified as the title compound.

Yield=240 mg, 1.28 mmol, 53%

[M+H]⁺=188.5

B. Diethylamino-acetic acid trifluoroacetate

Diethylamino-acetic acid tert-butyl ester (240 mg, 1.28 mmol) was dissolved in CH₂Cl₂ (4 mls). Trifluoroacetic acid (4 mls) was added. After 6 hours at room temperature the solvent was removed in vacuo giving a brown oil identified as the title compound.

Yield=310 mg, 1.26 mmol, 99%

[M+H]⁺=132.66

C. (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-(2-diethylamino-acetylamino)-3-(3,4-difluoro-phenyl)-propionamide ditrifluoroacetate

((S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-propionamide dihydrochloride (155 mg, 0.41 mmol) was dissolved in CH₂Cl₂ (20 mls) and DMF (2 mls). This solution was cooled to 0° C. Diethylamino-acetic acid trifluoroacetate (100 mg, 0.41 mmol) was added followed by HOBt (66 mg, 0.49 mmol) and water soluble carbodiimide (86 mg, 0.45 mmol). After 15 mins triethylamine (200 mg, 2.04 mmol) was added. After 4 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (150 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 10% MeOH, 90% CH₂Cl₂, fractions combined and evaporated in vacuo to give a colourless oil. The residue was further purified by Prep HPLC. (19×250 mm Sunfire C-18 Column) 0 to 60% 0.1% TFA/MeCN into 0.1% TFA/H₂O over 35 min at 20 ml/min. Fractions combined and freeze dried to give a white solid identified as the title compound.

Yield=60 mg, 0.09 mmol, 23%

[M+H]⁺=418.06

¹H NMR: (400 MHz) (CD₃OD) 1.26 (6H, t, J=6.9 Hz), 2.91-2.97 (1H, m), 3.10-3.21 (5H, m), 3.86-4.00 (2H, m), 4.22-4.34 (2H, m), 4.63-4.68 (1H, m), 6.97 (1H, d, J=9.2 Hz), 7.02-7.05 (1H, m), 7.12-7.23 (2H, m), 7.73 (1H, s), 7.77 (1H, dd, J=9.2, 2.0 Hz), 8.74 (1H, t, J=5.8 Hz).

Example 11 (S)-2-Amino-3-methyl-pentanoic acid [(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl]-amide

A. (R)-2-tert-Butoxycarbonylamino-3,3-dicyclohexyl-propionic acid

Boc-D-3,3-Diphenylalanine (4.86 g, 14.06 mmol) was dissolved in methanol (200 mls). This solution was hydrogenated over 5% Rh on carbon (500 mg) at 60 psi and room temperature. After 2 days at room temperature further 5% Rh on carbon (500 mg) was added and hydrogenation continued at 60 psi and room temperature for a further 3 days. After this time the catalyst was filtered off through celite and the residue washed with MeOH (100 mls). The combined filtrates were evaporated in vacuo to give a foamy white solid identified as the title compound,

Yield=4.95 g, 14 mmol, 100%

[M+H]⁺=354.28

B. {(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-carbamic acid tert-butyl ester

(R)-2-tert-Butoxycarbonylamino-3,3-dicyclohexyl-propionic acid (995 mg, 2.82 mmol) was dissolved in CH₂Cl₂ (30 mls). Triethylamine (712 mg, 7.04 mmol) and HBTU (1.07 g, 2.81 mmol) was added followed by 5-aminomethyl-pyridin-2-ylamine dihydrochloride (460 mg, 2.32 mmol). After 3 hours at room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 3% MeOH, 97% CHCl₃, fractions combined and evaporated in vacuo to give a colourless oil identified as the title compound.

Yield=872 mg, 1.90 mmol, 81%

[M+H]⁺=495.39

C. (R)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3,3-dicyclohexyl-propionamide ditrifluoroacetate

{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-carbamic acid tert-butyl ester (872 mg, 1.90 mmol) was dissolved in TFA (30 mls). After one hour at room temperature the solvent was removed to give a pale orange identified as the title compound.

Yield=1.105 g, 1.88 mmol, 99%

[M+H]⁺=359.30

D. ((S)-1-[(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethylcarbamoyl]-2-methyl-butyl)-carbamic acid tert-butyl ester

(R)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3,3-dicyclohexyl-propionamide ditrifluoroacetate (90 mg, 0.158 mmol) was dissolved in CH₂Cl₂ (20 mls) and DMF (2 mls). This solution was cooled to 0° C. Boc-Ile-OH (42 mg, 0.187 mmol) was added followed by HOBt (47 mg, 0.31 mmol) and water soluble carbodiimide (35 mg, 0.18 mmol). After 15 mins triethylamine (31 mg, 0.31 mmol) was added. After 18 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (50 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×20 mls), brine (1×20 mls), dried (Na₂SO₄) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 4% MeOH, 96% CHCl₃, fractions combined and evaporated in vacuo to give a colourless oil identified as the title compound.

Yield=73 mg, 0.13 mmol, 83%

[M+H]⁺=572.6

E. (S)-2-Amino-3-methyl-pentanoic acid {(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide ditrifluoroacetate

((S)-1-{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethylcarbamoyl}-2-methyl-butyl)-carbamic acid tert-butyl ester (65 mg, 0.11 mmol) was treated with TFA (20 mls). After one hour at room temp the solvent was evaporated in vacuo to give a colourless oil identified as the title compound. Freeze dried from water to give white solid. The residue was further purified by Prep HPLC. (19×250 mm Sunfire C-18 Column) 10 to 90% 0.1% TFA/MeCN into 0.1% TFA/H₂O over 35 min at 20 ml/min. Fractions combined and freeze dried to give a white solid identified as the title compound.

Yield 15 mg, 0.021 mmol, 19%

[M+H]⁺=472.4

¹H NMR: (270 MHz) (CD₃OD) 0.95-1.25 (18H, m), 1.52-1.70 (14H, m), 3.94 (1H, d, J=4.2 Hz), 4.19-4.27 (2H, m), 4.58 (1H, d, J=7.2 Hz), 4.90 (5H, s), 6.98 (1H, d, J=9.19 Hz), 7.79 (1H, d, J=1.5 Hz), 7.91 (1H, dd, J=2.9 Hz, 9.2Hz), 8.70-8.90 (1H, m)

TABLE 1 Compounds were synthesised as described for Examples 1 to 4

Example Stereochemistry Mol No Y of Y R¹ Wt [M + H]⁺ 12

S

443.33 444.4 13

R

511.27 512.5, 514.5 14

R

429.31 430.4 15

R

427.29 428.3 16

R

443.33 444.2 17

387.26 388.3 18

R

401.28 402.3 19

401.28 402.3 20

R

389.28 390.3 21

R

403.29 404.32 22

R

419.23 420.2 23

R

417.22 418.00 24

R

417.19 418.2, 420.2 25

R

451.22 452.2 26

R

383.23 384.2 27

R

397.25 398.3 28

R

397.25 398.3 29

R

401.22 402.3 30

R

451.22 452.2 31

R

408.23 409.3 32

R

419.21 420.4 33

R

401.22 402.1 34

R

433.25 434.2 35

R

451.15 452.4, 454.3 36

R

417.19 418.1, 420.2 37

R

399.23 400.1 38

R

437.20 438.1 39

R

419.21 420.26 40

R

422.24 423.2 41

R

439.20 440.24 42

R

465.24 466.2 43

R

433.23 434.28 44

R

415.24 416.00 45

R

431.21 432.1 46

R

431.21 432.2, 434.2 47

R

413.24 414.1 48

R

451.22 452.2 49

R

433.23 434.20 50

R

487.20 488.15 51

R

453.22 454.04 52

R

453.31 454.35 53

S

433.23 434.04 54

R

485.14 486.1, 488.2 55

R

435.12 435.9, 438.0 56

S

453.08 454.05 57

R

471.12 472.1, 474.0 58

S

471.12 472.1, 474.0 59

R

519.10 520.18, 522.18 60

R

499.15 500.20 61

R

451.15 452.19 62

R

423.12 423.9, 425.9 63

R

449.14 450.12, 452.12 64

R

497.14 498.1, 500.1 65

R

433.11 433.9, 460.0 66

R

471.10 472.1, 474.1 67

R

499.15 500.06 68

R

491.19 492.2, 494.2 69

409.11 409.96 70

R

519.16 519.95, 521.99 71

R

385.19 385.95 72

R

403.18 404.54 73

R

399.21 400.09 74

R

417.20 418.19 75

R

431.23 432.20 76

R

415.18 416.11 77

R

415.18 416.17 78

R

437.19 438.19 79

377.17 378.48 80

R

453.20 454.26 81

R

467.21 468.26 82

S

433.23 434.04 83

S

419.21 420.28 84

R

391.18 392.15 85

S

391.18 392.15 86

R

405.20 406.45 87

R

373.19 374.15 88

S

373.19 374.55 89

R

401.22 402.09

TABLE 2 Compounds were synthesised as described for Examples 1 to 7 and 9 and 10

Example Stereochemistry Mol No Y of Y R¹ Wt [M + H]+ 90

R

449.14 450.01 91

R

449.20 450.10 92

R

431.23 432.24 93

R

415.18 416.1, 418.20 94

R

435.19 436.1 95

R

437.19 438.03 96

R

417.20 418.22 97

R

471.17 472.15 98

R

399.21 400.07 99

R

399.21 400.09 100

R

411.23 412.11 101

R

381.22 382.16 102

R

437.28 438.19 103

R

415.18 416.52 104

R

395.23 396.55 105

R

395.23 396.19 106

R

395.23 396.20 107

R

411.23 412.91 108

R

399.21 400.12 109

R

415.18 416.12, 418.10 110

R

449.14 450.14, 452.10 111

R

449.48 450.53 112

R

382.47 383.56 113

R

420.52 421.54 114

R

432.52 433.1 115

R

387.26 388.18 116

S

417.20 418.08 117

R

477.17 478.10 118

R

459.26 460.16 119

R

427.24 428.20 120

R

443.21 444.45 121

R

423.26 424.60 122

R

423.26 424.20 123

R

423.26 424.21 124

R

439.26 440.21 125

R

427.24 428.22 126

R

443.98 444.20 127

R

478.43 478.55 128

R

477.53 478.62 129

R

410.52 411.60 130

R

448.57 449.38 131

R

431.59 432.57 132

R

445.23 446.61 133

R

459.24 460.61 134

R

475.20 476.24 135

R

461.19 462.21 136

R

413.50 414.54 137

R

409.94 410.59 138

R

429.95 430.19 139

R

427.52 428.58 140

R

493.23 494.23 141

R

525.17 526.04, 528.02 142

R

528.01 528.57 143

R

528.01 528.56 144

R

431.21 432.29 145

R

413.22 414.13 146

R

459.53 460.57 147

R

441.25 442.21 148

R

433.46 434.45 149

R

479.21 480.60 150

451.15 452.21, 454.20 151

R

465.17 465.86 152

499.15 500.05 153

423.12 424.09 154

465.17 465.89 155

R

507.22 508.13 156

419.21 420.30 157

447.24 448.61 158

447.24 448.56 159

475.57 476.63 160

467.21 468.55 161

481.23 482.55 162

493.23 494.58 163

501.17 502.52 164

501.17 502.54 165

501.17 502.59 166

497.22 498.57 167

433.23 434.52 168

433.23 434.53 169

473.26 474.62 170

431.21 432.60 171

433.19 434.41 172

479.21 480.54 173

479.21 480.53 174

453.20 454.51 175

R

433.49 434.50 176

S

433.49 434.51 177

S

447.53 448.56 178

R

447.24 448.59 179

R

447.24 448.61 180

R

415.24 416.51 181

S

415.24 416.60 182

R

429.25 430.59 183

R

429.54 430.58 184

R

495.24 496.29 185

R

481.55 482.51

TABLE 3 Compounds were synthesised as described for Examples 1 to 7 and 9 and 10

Stereo Example chem. Mol No Y At Y R¹ R⁸ R⁹ R¹⁰ Wt [M + H]+ 186

R

Me H H 443.33 444.3 187

R

Me H H 457.34 458.4 188

R

Me H H 479.19 480.20, 482.23 189

R

Me H H 449.14 450.7, 452.1 190

R

Me H H 463.15 464.11 191

R

Me H H 467.09 468.1 192

R

Me H H 485.12 486.13 193

R

Me H H 513.17 514.1 194

R

Me H H 517.14 518.1 195

R

Me H H 533.12 534.0, 536.6 196

R

Me H H 500.15 501.03 197

R

Me H H 485.14 486.18 198

R

Me H H 491.19 492.2 199

R

Me H H 465.17 466.2 200

R

Me H H 505.20 506.24 201

R

Me H H 463.15 464.16 202

R

Me H H 511.15 512.16 203

R

Me H H 461.28 462.23 204

R

Me H H 413.22 414.90 205

R

Me H H 431.21 432.16 206

R

Me Me H 445.52 446.56 207

R

Me Me H 461.56 462.54 208

R

Me Me H 471.36 472.30 209

R

H H Me 447.26 448.11

TABLE 4 Compounds were synthesised as described for Examples 8

Example Stereochemistry Mol No Q of Y R¹ Wt [M + H]+ 210

R

513.10 513.98 211

R

529.13 530.30 212

R

501.10 502.04 213

R

531.20 532.07

TABLE 5 Compounds were synthesised as described for Examples 1 to 7 and 9 to 11

Example Stereochemistry Mol No Y of Y Wt [M + H]⁺ 214

R 471.36 472.4 215

S 455.33 456.35 216

S 505.34 506.36 217

S 471.36 472.39 218

S 443.33 444.37 219

S 485.37 486.39 220

415.29 416.28 221

429.31 430.34 222

443.33 444.36 223

S 469.68 470.68

TABLE 6 Compounds were synthesised as described for Examples 1 to 11

Example Stereochemistry Mol No Y of Y R² R¹¹ Wt [M + H]⁺ 224

R OH H 399.49 400.3 225

R H Me 395.5 396.2

Example 226 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide

A. 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide trifluoroacetate

((S)-2-Amino-N-(6-amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-propionamide dihydrochloride (800 g, 2.11 mmol) was dissolved in CH₂Cl₂(100 mls). This solution was cooled to 0° C. 3-Methylpyrrole-2-carboxylic acid (264 mg, 2.11 mmol) was added followed by HOBt (399 mg, 2.95 mmol) and water soluble carbodiimide (486 mg, 2.53 mmol). After 15 mins triethylamine (640 g, 0.63 mmol) was added. After 18 hrs 0° C. to room temperature the reaction mixture was diluted with CHCl₃ (150 mls), this solution was washed with sat. NaHCO₃ (1×20 mls), water (1×50 mls), brine (1×50 mls), dried (Na₂SO₄) and filtered through PS paper and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 7% MeOH, 93% CHCl₃, fractions combined and evaporated in vacuo to give an orange oil. The residue purified by Prep HPLC. (19×250 mm Sunfire C-18 Column) 10 to 90% 0.1% TFA/MeCN into 0.1% TFA/H2O over 35 min at 20 ml/min. Fractions combined and freeze dried to give a pale pink solid identified as the title compound.

Yield=368 mg, 0.70 mmol, 33%

[M+H]⁺=414.22

¹H NMR: (CD₃OD, 400 MHz) 2.30 (3H, s) 2.81-3.25 (2H, m) 4.17-4.35 (2H, m) 4.71 (1H, t, J=8.0 Hz) 5.25 (4H, br s) 6.00 (1H, s) 6.74-6.78 (1H, m) 7.08-7.14 (3H, m) 7.73-7.77 (2H, m) 8.73-8.79 (1H, m) 10.56 (1H, s).

TABLE 7 Compounds were synthesised as described for Example 226

Example Mol No R¹⁶ R¹⁷ R¹⁸ R R¹ Wt [M + H]⁺ 227 H H H H

423.26 424.3 228 H H H H

413.19 414.3 229 H H H H

431.16 432.4 230 Me Me Me H

473.20 474.10 231 Me H Me H

441.22 442.27 232 Me H Me H

459.19 460.2 233 Me H Me H

459.12 460.1, 462.1 234 Me H Me H

405.22 406.1 235 Me H Me H

425.16 426.2, 428.2 236 Me H Me H

409.19 410.1 237 Me H Me H

391.20 392.22 238 Me H Me H

397.25 398.26 239 Me H Me H

425.16 425.92 240 Me H Me H

459.19 460.21 241 Me H Me H

430.21 431.1 242 Me H Me H

409.19 410.12 243 Me H Me H

427.18 428.1 244 Me H Me H

405.22 406.24 245 Me H Me H

445.17 446.21 246 Me H Me H

447.15 448.1, 450.1 247 Me H Me H

407.20 408.0 248 Me H Me H

445.17 446.1 249 Me H Me H

427.18 428.22 250 Me H Me H

447.17 448.16 251 Me H Me H

481.15 482.0 252 Me H Me H

467.23 468.18 253 Me H Me H

405.22 406.15 254 Me H Me H

421.21 422.15 255 Me H Me H

435.23 436.13 256 Me H Me H

447.26 448.21 257 Me H Me H

442.21 443.54 258 Me H Me H

445.17 446.18 259 H Me H H

411.15 412.13 260 H Me H H

395.18 396.15 261 Me H H H

395.18 396.14 262 Me H H H

411.15 412.41 263 Me H H H

445.11 446.38, 448.1 264 Me H H H

445.11 446.09, 448.1 265 Me H H H

395.18 396.44 266 Me H H H

411.15 412.39, 414.3 267 Me H H H

411.15 412.12 268 Me H H H

391.20 392.45 269 Me H H H

395.18 396.42 270 Me H H H

413.17 414.42 271 Me H H H

445.17 446.42 272 Me H H H

445.17 446.18 273 Me H H H

383.23 384.48 274 H H CO₂Me H

489.16 490.1 275 H H CO₂H H

475.15 476.20 276 Me H CO₂H H

489.16 490.17 277 Me H Me Me

473.20 474.1 278 Me H Me Me

455.23 456.22 279 Me H Me Me

439.18 440.18 280 Me H Me Me

473.14 474.2 281 Me H Me Me

419.23 420.25 282 Me H Me Me

473.20 474.20 283 Me H Me Me

444.23 445.31 284 Me H Me Me

441.20 442.20 285 Me H Me Me

423.21 424.15 286 Me H H Me

427.18 428.44

TABLE 8 Compounds were synthesised as described for Example 226

Example No Y R R¹ Mol Wt [M + H]⁺ 287

H

382.16 383.04 288

H

382.16 383.03 289

H

414.18 415.02 290

H

396.17 397.24 291

H

410.19 411.52 292

H

503.23 504.18 293

H

509.19 510.17 294

H

489.20 490.18 295

H

487.18 488.12 296

H

521.14 522.12, 524.12 297

H

487.18 488.13 298

H

463.20 464.4 299

H

464.2 465.2 300

H

493.21 494.2 301

H

481.19 482.2 302

H

479.20 480.2 303

Me

477.22 478.23 304

Me

507.23 508.24 305

Me

495.21 496.3 306

H

477.22 478.3 307

H

481.17 482.5 308

H

511.18 512.3 309

Me

495.19 496.11 310

Me

525.20 526.19 311

H

431.18 432.2 312

H

461.19 462.2 313

H

447.15 448.2, 550.2 314

H

477.16 478.2, 480.2 315

Me

461.16 462.16 316

Me

491.17 492.23 317

H

427.20 428.20 318

H

457.21 458.20 319

Me

441.22 442.25 320

Me

495.12 496.18 321

Me

525.13 526.22 322

Me

495.19 496.2 323

H

449.17 450.2 324

H

467.16 468.10 325

H

449.17 449.88, 451 326

H

467.16 468.08 327

H

479.18 480.09 328

H

450.16 451.19 329

H

503.14 504.1 330

H

431.18 432.12 331

H

449.17 450.21 332

H

461.19 462.22 333

H

432.17 433.21 334

H

443.20 444.17 335

H

469.16 470.19 336

Me

466.21 467.1 337

Me

496.22 497.1 338

H

419.23 420.17

TABLE 9 Compounds were synthesised as described for Examples 1 to 4

Example Stereochemistry Mol No Y of Y R¹ Wt [M + H]⁺ 339

S

403.29 404.57 340

R

415.24 416.20 341

R

417.19 417.99 342

R

465.19 465.91

TABLE 10 Compounds were synthesised as described for Examples 1 to 7 and 9 and 10

Example Stereochem- Mol No Y istry of Y R¹ Wt [M + H]⁺ 343

S

487.28 488.61 344

S

405.20 406.49 345

S

419.21 420.53 346

S

433.23 434.48 347

S

447.24 448.57 348

S

461.26 462.61 349

S

475.28 476.58 350

S

461.26 462.54 351

S

481.23 482.48 352

S

495.24 495.56 353

S

475.28 476.58 354

S

445.23 446.23 355

S

433.23 434.39 356

S

431.21 432.11 357

R

431.21 432.15 358

R

447.24 448.22 359

R

433.23 434.03 360

S

449.22 450.46 361

S

435.21 436.17 362

S

449.22 450.47 363

R

449.22 450.45 364

S

491.23 492.25 365

459.24 460.51 366

417.20 418.29 367

S

401.22 402.40 368

S

415.24 416.57 369

S

429.25 430.57 370

S

443.27 444.59 371

S

457.29 458.62 372

S

443.27 444.55 373

S

491.27 492.62 374

S

427.24 428.51 375

R

427.24 428.50 376

S

415.24 416.51 377

R

429.25 430.51 378

441.25 442.52 379

413.22 414.47 380

401.22 402.32 381

S

403.29 404.57 382

S

387.26 388.53 383

S

403.29 404.56 384

S

389.28 390.27 385

S

431.33 432.57 386

S

391.26 392.25 387

S

405.27 406.26 388

S

419.29 420.27 389

S

419.29 420.26 390

S

403.29 404.55 391

S

375.26 376.50 392

429.31 430.57 393

417.31 418.53 394

471.36 472.67 395

S

457.34 458.64 396

R

441.31 442.60 397

R

505.34 506.66 398

R

479.19 480.14, 482.12 399

R

465.17 466.19 400

R

513.17 514.11, 516.10 401

S

465.17 466.35 402

R

477.17 478.44 403

S

477.17 478.73 404

463.15 464.41 405

R

445.22 446.48, 448.40 406

R

431.21 432.20 407

R

479.21 480.17 408

S

417.19 417.94 409

S

431.21 432.20 410

S

431.21 432.20 411

S

443.21 444.45 412

429.19 430.44 413

S

397.25 398.24 414

S

411.26 412.27 415

S

411.26 412.27 416

S

451.22 452.20 417

S

465.24 466.01 418

S

465.52 466.62 419

R,S

477.24 478.49 420

463.22 464.47 421

R

477.24 478.51 422

S

477.24 478.51 423

463.22 464.48 424

R

447.24 448.50 425

R,S

445.23 446.48, 448.40 426

457.22 458.49, 460.48 427

S

363.26 364.51

TABLE 11 Compounds were synthesised as described for Examples 1 to 7 and 9 and 10

Stereo- Example chem. Mol No Y At Y R¹ R⁸ R⁹ R¹⁰ Wt [M + H]⁺ 428

Me H H 415.24 416.20 429

Me H H 473.26 474.53 430

Me H H 445.23 446.49 431

R

Me H H 459.24 460.50 432

S

Me H H 429.50 460.50

TABLE 12 Compounds were synthesised as described for Examples 1 to 7 and 9 to 11

Stereo- Example chemistry No Y of Y Mol Wt [M + H]⁺ 433

S 485.37 486.66 434

S 405.20 406.49

TABLE 13 Compounds were synthesised as described for Examples 1 to 11

Stereo- Example chemistry No Y of Y R² R¹¹ Mol Wt [M + H]⁺ 435

S OH H 419.29 420.57 436

S Me H 417.31 418.50 437

S H Me 417.31 418.49 438

S H Me 417.31 418.46 439

S H Me 431.33 432.57

TABLE 14 ¹H NMR data for examples Example Frequency No Solvent (MHz) Chemical Shifts 12 CD₃OD 270 0.95-1.05 (6H, m), 1.10-2.10 (28H, m), 3.78-3.82 (1H, m), 4.25-4.34 (3H, m), 6.92-6.98 (1H, m), 7.61-7.84 (2H, m) 13 CD₃OD 270 0.90-1.96 (22H, m), 2.70-2.98 (2H, m), 3.09-3.18 (4H, m), 4.05-4.20 (2H, m), 6.96 (1H, d, J = 9.1 Hz), 7.22-7.30 (4H, m), 7.72 (1H, s), 7.80-7.90 (2H, m) 16 CD₃OD 270 1.00 (6H, d), 1.13-2.1 (28H, m), 3.75-3.95 (1H, m), 4.15-4.35 (2H, m), 6.97 (1H, d, J = 8.9 Hz), 7.72 (1H, s), 7.86 (1H, d, J = 8.7 Hz), 8.80-8.90 (1H, m) 19 CD₃OD 270 1.19-1.78 (23H, m), 2.71 (3H, s), 3.83 (2H, s), 4.26-4.32 (3H, m), 6.97 (1H, d, J = 9.1 Hz), 7.74 (1H, s), 7.84-7.87 (1H, m), 8.85 (1H, s, br) 20 CD₃OD 270 0.99-1.14 (8H, m), 1.21-1.32 (6H, m), 1.40-1.71 (6H, m), 3.19-3.21 (2H, m), 3.76 (1H, d, J = 5.2 Hz), 4.27-4.39 (3H, m), 4.91 (5H, s), 6.97 (1H, d, J = 9.4 Hz), 7.74 (1H, s), 7.86 (1H, d, J = 8.2 Hz), 8.70-8.90 (1H, m) 21 CD₃OD 270 0.9-1.0 (7H, m), 1.4-1.8 (7H, m), 2.4-2.6 (5H, m), 3.3-3.7 (10H, m), 4.0-4.4 (3H, m) 6.9-7.0 (1H, d, J = 7 hz), 7.8-7.9 (2H, m), 8.7-8.9 (2H, m) 22 CD₃OD 270 0.65 (3H, d, J = 6.9 Hz), 0.86 (3H, d, J = 6.9 Hz), 1.28-1.29 (1H, m), 1.88-1.91 (1H, m), 3.30-3.56 (3H, m), 3.66-3.68 (3H, m), 4.08-4.19 (2H, m), 4.63-4.85 (3H, m), 6.85-6.89 (1H, m), 7.33-7.37 (2H, m), 7.46-7.59 (4H, m), 7.75-7.71 (1H, m), 7.84-7.87 (1H, m), 8.18 (1H, d, J = 7.6 Hz) 24 CD₃OD 270 0.81-0.83 (6H, m), 1.10-1.30 (2H, m), 2.95-3.20 (1H, m), 3.27-3.30 (3H, m), 3.71 (1H, d, J = 5.2 Hz), 4.21 (2H, s), 4.7-4.9 (1H, m), 4.91 (4H, s), 6.94 (1H, d, J = 9.1 Hz), 7.21-7.36 (4H, m), 7.68 (1H, s), 7.76 (1H, d, J = 9.4 Hz), 8.5-8.7 (1H, s, br) 25 CD₃OD 270 0.81-0.87 (6H, m), 1.27-1.30 (2H, m), 3.19-3.29 (1H, m), 3.30-3.31 (3H, m), 3.73 (1H, d, J = 5.2 Hz), 4.21-4.22 (2H, m), 4.71-4.77 (1H, m), 4.91 (4H, s), 6.94 (1H, d, J = 9.1 Hz), 7.42-7.52 (3H, m), 7.66-7.69 (2H, s), 7.74-7.79 (1H, m), 8.5-8.7 (1H, s, br) 26 CD₃OD 270 0.75-0.80 (6H, m), 1.10-1.30 (1H, m), 1.60-1.85 (1H, m), 2.83-2.92 (1H, m), 3.14-3.21 (1H, m), 3.68 (1H, d, J = 5.2 Hz), 4.22-4.26 (2H, m), 4.65-4.67 (1H, m), 4.90 (6H, s), 6.94 (1H, d, J = 8.8 Hz), 7.21-7.27 (5H, m), 7.68-7.76 (2H, m), 8.60-8.80 (1H, m) 27 CD₃OD 270 0.77 (6H, t, J = 7.28 Hz), 1.10-1.40 (1H, m), 1.60-1.80 (1H, m), 2.29 (3H, s), 2.75-2.95 (1H, m) 3.12-3.28 (1H, m), 3.29-3.31 (2H, m), 3.68 (1H, d, J = 5.1 Hz), 4.22-4.26 (2H, m), 4.62-4.64 (1H, m), 4.90 (5H, s), 6.92-7.15 (4H, m), 7.69-7.75 (2H, m), 8.65-8.90 (1H, m) 28 CD₃OD 270 0.83 (6H, t, J = 6.6 Hz), 0.90-1.10 (1H, m), 1.60-1.80 (1H, m), 2.34 (3H, s), 2.85-3.00 (1H, m), 3.12-3.28 (1H, m), 3.29-3.31 (2H, m), 3.71 (1H, d, J = 5.4 Hz), 4.16-4.23 (2H, m), 4.63-4.68 (1H, m), 4.90 (5H, s), 6.92 (1H, d, J = 9.2 Hz), 7.06-7.14 (3H, m), 7.63-7.69 (2H, m), 8.65-8.90 (1H, m) 29 CD₃OD 270 0.77-0.82 (7H, m), 1.17-1.30 (1H, m), 1.6-1.8 (1H, m), 2.91-2.95 (1H, m), 3.29-3.30 (1H, m), 3.68 (1H, d, J = 5.2 Hz), 4.22-4.27 (2H, m), 4.62-4.66 (1H, m), 4.91 (4H, s), 6.94-7.09 (4H, m), 7.28-7.31 (2H, m), 7.71-7.79 (2H, m), 8.5-8.7 (1H, m) 30 CD₃OD 270 0.72-0.77 (7H, m), 1.17-1.30 (1H, m), 1.6-1.8 (1H, m), 2.98-3.05 (1H, m), 3.25-3.30 (1H, m), 3.66 (1H, d, J = 5.2 Hz), 4.26 (2H, s), 4.71-4.77 (1H, m), 4.91 (4H, s), 6.95 (1H, d, J = 9.1 Hz), 7.51-7.59 (4H, m), 7.73 (1H, s), 7.75-7.80 (1H, m), 8.5-8.7 (1H, s, br) 31 CD₃OD 270 0.70-1.05 (7H, m), 1.10-1.30 (1H, m), 1.60-1.80 (1H, m), 2.90-3.10 (1H, m), 3.20-3.40 (2H, m), 3.69 (1H, d, J = 5.18 Hz), 4.20-4.40 (2H, m), 4.65-4.75 (1H, m), 4.90-5.10 (4H, m), 6.97 (1H, d, J = 9.15 Hz), 7.40-7.90 (6H, m), 8.70-8.90 (1H, m) 32 CD₃OD 270 0.75-1.30 (8H, m), 1.65-1.80 (1H, m), 2.80-2.95 (1H, m), 3.10-3.20 (1H, m), 3.25-3.35 (2H, m), 3.60-3.80 (2H, m), 4.15-4.35 (2H, m), 4.65-4.80 (1H, m), 4.90-5.10 (3H, m), 6.90-7.20 (4H, m), 7.70-7.85 (2H, m) 33 CD₃OD 270 0.70-1.00 (6H, m), 1.10-1.30 (1H, m), 1.60-1.80 (1H, m), 2.80-2.95 (1H, m), 3.10-3.20 (1H, m), 3.25-3.35 (2H, m), 3.65-3.75 (1H, m), 4.15-4.40 (2H, m), 4.50-4.70 (1H, m), 4.80-5.00 (4H, m), 6.90-7.10 (3H, m), 7.20-7.30 (2H, m), 7.65-7.80 (2H, m), 8.70-8.90 (1H, m) 34 CD₃OD 270 0.48 (3H, t, J = 7.13 Hz) 0.65-0.80 (3H, m), 1.00-1.20 (1H, m), 1.55-1.70 (1H, m), 3.00-3.10 (1H, m), 3.25-3.40 (2H, m), 3.60-3.80 (2H, m), 4.10-4.35 (2H, m), 4.80-4.95 (1H, m), 4.95-5.05 (4H, m), 6.74 (1H, d, J = 9.15 Hz), 7.30-7.85 (9H, m), 8.70-8.80 (1H, m) 35 CD₃OD 270 0.70-0.90 (7H, m), 1.15-1.30 (1H, m), 1.65-1.80 (1H, m), 2.80-2.95 (1H, m), 3.10-3.20 (1H, m), 3.25-3.35 (2H, m), 3.60-3.80 (2H, m), 4.15-4.35 (2H, m), 4.70-4.80 (1H, m), 4.90-5.10 (3H, m), 6.90-7.00 (1H, m), 7.15-7.25 (1H, m), 7.35-7.50 (2H, m), 7.70-7.80 (2H, m) 36 CD₃OD 270 0.80-0.89 (6H, m), 1.18 (1H, br, s), 1.71 (1H, br, s), 2.88-2.91 (1H, m), 3.14-3.21 (1H, m), 3.70 (1H, d, J = 4.7 Hz), 4.25 (1H, s), 4.63 (1H, t, J = 3.9 Hz), 4.91 (7H, s), 6.96 (1H, d, J = 8.9 Hz), 7.26 (4H, s), 7.72-7.78 (2H, m), 8.75 (1H, s) 37 CD₃OD 270 0.81 (6H, s), 1.24 (1H, s), 1.73 (1H, s), 2.74-2.83 (1H, m), 3.06-3.11 (1H, m), 3.31 (1H, s), 3.71 (1H, s), 4.24 (1H, s), 4.57 (1H, br, s), 4.91 (7H, s), 6.69 (2H, d, J = 6.9 Hz), 6.94 (1H, d, J = 8.6 Hz), 7.05 (2H, d, J = 6.9 Hz), 7.73 (2H, d, J = 9.7 Hz) 38 CD₃OD 270 0.84-0.86 (6H, m), 1.24-1.29 (1H, m), 1.77-1.79 (1H, m), 2.91-2.99 (1H, m), 3.14-3.19 (1H, m), 3.30 (1H, s), 3.73 (1H, d, J = 4.9 Hz), 4.24 (2H, s), 4.71 (1H, t, J = 3.5 Hz), 4.90 (5H, s), 6.95 (1H, d, J = 9.1 Hz), 7.09-7.19 (2H, m) 7.74-7.83 (2H, m), 8.75-8.78 (1H, m) 39 CD₃OD 270 0.80-0.85 (6H, m), 1.25 (1H, s), 1.74 (1H, s), 2.92 (1H, s), 3.19-3.32 (2H, m), 3.71-3.73 (1H, m), 4.27 (2H, s), 4.69 (1H, t, J = 5.2 Hz), 4.93 (6H, s), 6.89-6.99 (4H, m), 7.75-7.84 (2H, m) 40 CD₃OD 270 0.60-0.80 (6H, m), 1.10-1.30 (1H, m), 1.60-1.75 (1H, m), 3.00-3.15 (1H, m), 3.20-3.40 (2H, m), 3.69 (1H, d, J = 5.42 Hz), 4.10-4.30 (2H, m), 4.65-4.80 (2H, m), 4.90-5.10 (6H, m), 6.80-6.90 (1H, m), 6.95-7.20 (3H, m), 7.30-7.40 (1H, m), 7.50-7.60 (3H, m), 8.60-8.70 (1H, m) 41 CD₃OD 270 0.77-0.91 (5H, m), 1.23 (1H, s), 1.71 (1H, s), 3.17-3.31 (2H, m), 3.41-3.46 (1H, m), 3.72 (1H, s), 4.22 (2H, s), 4.82-4.91 (7H, m), 6.88 (1H, d, J = 7.9 Hz), 7.37 (3H, s), 7.65 (2H, s), 7.87 (2H, s), 8.75 (1H, s) 42 CD₃OD 270 0.65-0.85 (7H, m), 1.15-1.30 (1H, m), 1.65-1.80 (1H, m), 2.60 (3H, s), 2.90-3.10 (1H, m), 3.20-3.40 (3H, m), 3.61 (1H, d, J = 4.94 Hz), 4.20-4.40 (2H, m), 4.65-4.90 (1H, m), 4.90-5.10 (2H, m), 6.96 (1H, d, J = 9.15 Hz), 7.45-7.90 (6H, m), 8.75-8.90 (1H, m) 43 CD₃OD 270 0.70-0.95 (7H, m), 1.20-1.40 (1H, m), 1.70-1.90 (1H, m), 2.50-2.70 (3H, m), 2.85-2.95 (1H, m), 3.05-3.20 (1H, m), 3.25-3.35 (2H, m), 3.60-3.70 (1H, m), 4.15-4.30 (2H, m), 4.55-4.70 (1H, m), 4.90-5.00 (2H, m), 6.90-7.30 (4H, m), 7.70-7.90 (2H, m), 8.70-8.80 (1H, m) 44 CD₃OD 270 0.70-0.90 (7H, m), 1.20-1.35 (1H, m), 1.65-1.85 (1H, m), 2.60 (3H, s), 2.80-2.95 (1H, m), 3.05-3.20 (1H, m), 3.25-3.40 (2H, m), 3.63 (1H, d, J = 4.94 Hz), 4.20-4.35 (2H, m), 4.55-4.70 (1H, m), 4.90-5.10 (2H, m), 6.90-7.10 (3H, m), 7.20-7.35 (2H, m), 7.70-7.85 (2H, m), 8.70-8.85 (1H, m) 45 CD₃OD 270 0.70-0.90 (7H, m), 1.20-1.40 (1H, m), 1.60-1.75 (1H, m), 2.60 (3H, s), 2.80-2.95 (1H, m), 3.10-3.20 (1H, m), 3.25-3.40 (2H, m), 3.63 (1H, d, J = 4.70 Hz), 4.20-4.40 (2H, m), 4.60-4.70 (1H, m), 4.90-5.10 (2H, m), 6.90-7.10 (1H, m), 7.15-7.40 (4H, m), 7.70-7.85 (2H, m), 8.70-8.90 (1H, m) 46 CD₃OD 270 0.82 (6H, s), 1.28 (1H, s), 1.77 (1H, s), 2.60 (3H, s), 2.86-2.95 (1H, m), 3.11-3.18 (1H, m), 3.65 (1H, s), 4.25 (2H, s), 4.63 (1H, t, J = 6.2 Hz), 4.92 (5H, s), 6.97 (1H, d, J = 9.2 Hz), 7.27 (4H, s), 7.76 (2H, d, J = 9.4 Hz), 8.78 (1H, s) 48 CD₃OD 270 0.84-0.96 (6H, m), 1.34-1.38 (1H, m), 1.78-1.83 (1H, m), 2.61 (3H, s), 2.95-3.03 (3H, m), 3.68 (1H, d, J = 4.7 Hz), 4.24 (2H, s), 4.64-4.70 (1H, m), 4.91 (5H, s), 6.95 (1H, d, J = 9.2 Hz), 7.11-7.21 (2H, m), 7.75-7.82 (2H, m) 50 CD₃OD 270 0.8-0.9 (6H, m), 1.2-1.4 (1H, m), 1.6-1.9 (1H, m), 2.4-2.6 (7H, m), 2.9-3.2 (2H, m), 3.7-3.8 (1H, m), 4.0-4.4 (1H, m), 4.6-4.8 (1H, m), 6.85 (1H, d, J = 7 Hz), 7.8-8.0 (3H, m), 8.8-8.9 (1H, m), 9.15 (1H, d, J = 7 Hz) 51 CD₃OD 270 0.78 (7H, s), 1.28 (1H, s), 1.76 (1H, s), 2.61 (3H, s), 3.21-3.44 (3H, m), 3.67 (1H, s), 4.22 (2H, s), 4.82-4.94 (4H, m), 6.89 (1H, d, J = 9.4 Hz), 7.39 (3H, s), 7.67 (2H, s), 7.88 (2H, s), 8.81 (1H, s) 52 CD₃OD 270 0.6-0.8 (6H, m), 1.0-1.1 (1H, m), 1.3 (9H, s), 1.7-1.8 (1H, m), 2.4-2.6 (6H, m), 2.7-2.9 (1H, m), 3.0-3.2 (1H, m), 3.5-3.8 (1H, m), 4.1-4.2 (2H, m), 4.5-4.6 (1H, m), 6.95 (1H, d, J = 8 Hz), 7.1-7.3 (4H, m), 7.8-7.9 (2H, m), 8.3 (1H, m), 8.8-8.9 (2H, m) 53 CD₃OD 400 0.85-1.00 (6H, m), 1.10-1.30 (1H, m), 1.50-1.70 (1H, m), 1.85-1.95 (1H, m), 2.47 (2H, s), 2.90-3.10 (2H, m), 3.25-3.35 (1H, m), 3.625 (1H. d, J = 4 Hz), 4.10-4.30 (2H, m), 4.67 (1H, t, J = 8 Hz), 4.85-5.00 (2H, m), 6.90-7.00 (2H, m), 7.05-7.30 (2H, m), 7.70-7.80 (2H, m), 8.70-8.80 (1H, m) 54 CD₃OD 270 2.70-3.10 (4H, m), 3.20-3.40 (2H, m), 4.00-4.35 (3H, m), 4.40-4.45 (1H, m), 4.80-5.10 (3H, m), 6.90-7.50 (9H, m), 7.60-7.80 (2H, m), 8.60-8.80 (1H, m) 55 CD₃OD 270 1.60-2.10 (3H, m), 2.20-2.40 (1H, m), 2.80-3.50 (5H, m), 4.10-4.35 (3H, m), 4.55-4.85 (1H, m), 4.80-5.10 (3H, m), 6.90-7.00 (1H, m), 7.10-7.25 (1H, m), 7.30-7.50 (2H, m), 7.70-7.90 (2H, m), 8.70-8.90 (1H, m) 56 CD₃OD 270 2.90-3.00 (2H, m), 3.05-3.20 (1H, m), 3.25-3.40 (3H, m), 4.10-4.35 (4H, m), 4.40-4.50 (1H, m), 4.60-4.70 (1H, m), 4.90-5.10 (3H, m), 6.90-7.00 (1H, m), 7.10-7.20 (1H, m), 7.30-7.50 (2H, m), 7.70-7.80 (2H, m) 57 CD₃OD 270 2.65-2.80 (1H, m), 3.00-3.20 (1H, m), 3.25-3.40 (3H, m), 4.10-4.40 (2H, m), 4.60-4.70 (1H, m), 4.90-5.00 (2H, m), 6.80-6.90 (1H, m), 6.95-7.05 (1H, m), 7.10-7.20 (2H, m), 7.25-7.50 (5H, m), 7.70-7.80 (2H, m), 8.70-8.80 (1H, m) 58 CD₃OD 270 2.90-3.10 (2H, m), 3.25-3.40 (3H, m), 3.90-4.25 (2H, m), 4.50-4.65 (1H, m), 4.90-5.20 (2H, m), 6.85-7.00 (1H, m), 7.05-7.15 (1H, m), 7.20-7.80 (9H, m), 8.50-8.60 (1H, m) 59 CD₃OD 270 2.70-3.10 (4H, m) 3.20-3.40 (2H, m), 4.05-4.35 (3H, m), 4.50-4.60 (1H, m), 4.80-5.00 (3H, m), 6.90-7.50 (8H, m), 7.65-7.80 (2H, m), 8.70-8.80 (1H, m) 60 CD₃OD 270 2.64 (3H, s), 2.70-2.90 (2H, m), 2.95-3.15 (2H, m), 3.25-3.40 (2H, m), 3.95-4.40 (4H, m), 4.90-5.10 (2H, m), 6.90-7.30 (9H, m), 7.65-7.75 (2H, m), 8.70-8.80 (1H, m) 61 CD₃OD 270 0.89 (9H, s), 2.85-3.00 (1H, m), 3.10-3.20 (1H, m), 3.25-3.35 (2H, m), 3.54 (1H, s), 4.10-4.25 (2H, m), 4.60-4.70 (1H, m), 4.90-5.10 (3H, m), 6.90-7.10 (1H, m), 7.15-7.25 (1H, m), 7.35-7.45 (2H, m), 7.70-7.80 (2H, m), 8.70-8.80 (1H, m) 62 CD₃OD 270 1.35 (3H, d, J = 6.94 Hz), 2.62 (3H, s), 2.85-2.95 (1H, m), 3.05-3.15 (1H, m), 3.25-3.40 (2H, m), 3.70-3.90 (1H.m), 4.10-4.30 (2H, m), 4.50-4.70 (1H, m), 4.90-5.10 (2H, m), 6.90-7.00 (1H, m), 7.10-7.20 (1H, m), 7.25-7.50 (2H, m), 7.65-7.80 (2H, m), 8.70-8.80 (1H, m) 63 CD₃OD 270 1.46-1.63 (2H, m) 1.83 (2H, d, J = 10.9 Hz) 2.00 (1H, d, J = 14.1 Hz) 2.83-2.97 (2H, m) 3.10-3.18 (1H, m) 3.30-3.37 (1H, m) 3.79 (1H, dd, J = 8.6, 3.0 Hz) 4.21 (2H, q, J = 7.7 Hz) 4.59-4.65 (1H, m) 4.93 (6H, s) 6.94 (1H, d, J = 9.2 Hz) 7.16 (1H, dd, J = 8.2, 2.0 Hz) 7.37-7.42 (2H, m) 7.71-7.76 (2H, m) 64 CD₃OD 270 2.75-3.00 (2H, m), 3.16-3.25 (2H, m), 3.25-3.40 (2H, m), 4.10-4.40 (5H, m), 4.65-4.80 (1H, m), 4.90-5.00 (2H, m), 6.90-7.00 (1H, m), 7.15-7.50 (7H, m), 7.70-7.80 (2H, m), 8.70-8.85 (1H, m) 65 CD₃OD 270 2.95-3.15 (2H, m), 3.25-3.35 (1H, m), 4.00-4.35 (4H, m), 4.55-4.70 (1H, m), 4.80-5.00 (3H, m), 5.05-5.15 (1H, m), 5.70-5.85 (1H, m), 5.95-6.10 (1H, m), 6.90-7.05 (1H, m), 7.10-7.20 (1H, m), 7.30-7.50 (2H, m), 7.65-7.80 (2H, m), 8.70-8.85 (1H, m) 66 CD₃OD 270 2.20-2.50 (1H, m), 2.75-3.00 (2H, m), 3.05-3.20 (1H, m), 3.25-3.40 (2H, m), 3.65-3.80 (2H, m), 4.10-4.35 (2H, m), 4.50-4.75 (2H, m), 4.80-5.10 (2H, m), 6.90-7.05 (1H, m), 7.10-7.20 (1H, m), 7.30-7.50 (2H, m), 7.65-7.80 (2H, m), 8.70-8.85 (1H, m) 67 CD₃OD 270 0.80-2.00 (2H, m), 2.30-2.50 (2H, m), 2.80-2.95 (1H, m), 3.10-3.20 (1H, m), 3.25-3.35 (2H, m), 3.85-3.95 (1H, m), 4.15-4.40 (2H, m), 4.60-4.70 (1H, m), 4.90-5.10 (3H, m), 6.90-7.50 (9H, m), 7.70-7.85 (2H, m), 8.70-8.85 (1H, m) 68 CD₃OD 270 0.70-0.95 (2H, m), 1.00-1.30 (4H, m), 1.40-1.80 (7H, m), 2.80-2.95 (1H, m), 3.10-3.40 (3H, m), 3.80-3.90 (1H, m), 4.15-4.35 (2H, m), 4.60-4.70 (1H, m), 4.80-5.10 (3H, m), 6.90-7.00 (1H, m), 7.15-7.25 (1H, m), 7.35-7.50 (2H, m), 7.70-7.85 (2H, m), 8.70-8.85 (1H, m) 70 CD₃OD 270 2.75-3.20 (4H, m), 3.05-3.15 (2H, m), 4.05-4.25 (3H, m), 4.50-4.65 (1H, m), 4.85-5.00 (4H, m), 6.90-7.75 (11H, m) 72 CD₃OD 270 1.70-1.77 (1H, m), 1.85-1.94 (1H, m), 1.98-2.04 (1H, m), 2.29-2.38 (1H, m), 2.89-2.95 (1H, m), 3.11-3.17 (1H, m), 3.31-3.37 (2H, m), 4.16-4.20 (1H, m), 4.26-4.30 (2H, m), 4.64 (1H, dd, J = 6.56, 8.92), 4.86 (4H, s), 6.96 (1H, d, J = 9.1 Hz), 7.02-7.04 (1H, m), 7.11-7.20 (3H, m), 7.76-7.79 (1H, m), 8.60-8.75 (1H, m) 73 CD₃OD 270 1.44-1.61 (3H, m), 1.81-2.03 (3H, m), 3.13-3.18 (1H, m), 3.30-3.37 (1H, m), 3.77 (1H, dd, J = 8.6, 3.2 Hz), 4.21 (2H, s), 4.56-4.62 (1H, m), 4.92 (3H, br, s), 6.92-7.01 (3H, m), 7.20-7.25 (2H, m), 7.69-7.76 (2H, m), 8.6 1-8.68 (2H, m) 74 CD₃OD 270 1.37-1.94 (7H, m), 2.80-2.83 (3H, m), 2.87-2.91 (1H, m), 3.30-3.32 (1H, m), 3.76-3.80 (1H, m), 4.22 (2H, m), 4.60-4.65 (1H, m), 4.99 (2H, s) 6.93-7.19 (4H, m), 7.71-7.79 (2H, m), 8.66-8.69 (1H, m) 75 CD₃OD 270 1.08-1.10 (2H, d, J = 6.5 Hz), 1.54-1.58 (2H, m), 1.78-1.94 (3H, m), 2.94 (1H, s), 3.28-3.33 (3H, m), 3.66-3.80 (3H, m), 4.12-4.22 (3H, m), 4.79-4.82 (1H, m), 6.84 (1H, d, J = 2.2 Hz), 7.34-7.36 (3H, m), 7.45-7.58 (4H, m), 7.59-7.61 (1H, m), 7.73-7.77 (1H, m), 8.16 (1H, d, J = 8.2 Hz) 76 CD₃OD 270 1.36-1.61 (3H, m), 1.81-1.84 (2H, m), 1.97-2.02 (1H, m), 2.98-3.07 (2H, m), 3.30-3.38 (3H, m), 3.76-3.82 (1H, m), 4.21 (1H, s), 4.75-4.80 (1H, m), 4.92 (5H, s), 6.94 (1H, d, J = 9.02 Hz), 7.19-7.38 (4H, m), 7.68 (1H, s) 7.75-7.79 (1H, m) 77 CD₃OD 270 1.39-1.84 (6H, m), 1.93-1.98 (1H, m), 2.83-3.01 (1H, m), 3.14-3.19 (1H, m), 3.21-3.30 (1H, m), 3.76-3.81 (1H, m) 4.23 (1H, s) 4.62-4.65 (1H, m) 4.93 (5H, br, s), 6.94 (1H, d, J = 8.9 Hz), 7.15-7.25 (4H, m), 7.69-7.77 (1H, m), 8.66-8.73 (1H, m) 78 CD₃OD 270 1.36-1.95 (6H, m), 3.14-3.17 (1H, m), 3.19-3.22 (1H, m), 3.29-3.42 (2H, m), 3.76-3.80 (1H, m), 4.18 (2H, d, J = 8.2 Hz), 4.75-4.79 (1H, m), 4.95 (5H, br, s), 6.86 (1H, dd, J = 8.2, 1.0 Hz), 7.30-7.39 (3H, m), 7.61-7.66 (2H, m), 7.82-7.86 (2H, m) 80 CD₃OD 400 2.70-2.80 (1H, m), 2.85-3.00 (2H, m), 3.05-3.15 (1H, m), 3.25-3.40 (3H, m), 4.05-4.30 (3H, m), 4.40-4.60 (1H, m), 4.80-5.10 (3H, m), 6.90-7.20 (6H, m), 7.25-7.40 (3H, m), 7.65-7.80 (2H, m) 81 CD₃OD 400 2.70-2.80 (1H, m), 2.85-2.95 (3H, m), 3.00-3.15 (1H, m), 3.33 (3H, s), 4.05-4.30 (4H, m), 4.40-4.60 (1H, m), 4.80-5.00 (2H, m), 6.85-7.20 (6H, m), 7.25-7.45 (3H, m), 7.65-7.80 (2H, m), 8.65-8.80 (1H, m) 82 CD₃OD 400 0.85-1.00 (6H, m), 1.10-1.30 (1H, m), 1.50-1.70 (1H, m), 1.85-1.95 (1H, m), 2.47 (2H, s), 2.90-3.10 (2H, m), 3.25-3.35 (1H, m), 3.625 (1H, d, J = 4 Hz), 4.10-4.30 (2H, m), 4.67 (1H, t, J = 8 Hz), 4.85-5.00 (2H, m), 6.90-7.00 (2H, m), 7.05-7.30 (2H, m), 7.70-7.80 (2H, m), 8.70-8.80 (1H, m) 83 CD₃OD 400 0.90-1.10 (6H, m), 1.15-1.25 (1H, m), 1.45-1.60 (1H, m), 1.85-2.00 (1H, m), 2.90-3.10 (2H, m), 3.30-3.40 (2H, m), 3.70-3.80 (1H, m), 4.05-4.25 (2H, m), 4.56 (1H, t, J = 8 Hz), 4.80-5.10 (3H, m), 6.90-7.25 (4H, m), 7.60-7.80 (2H, m), 8.70-8.80 (1H, m) 84 CD₃OD 400 1.34 (3H, d, J = 7.0 Hz), 2.65 (3H, s), 2.86-3.01 (1H, m), 3.06-3.19 (1H, m), 3.65-3.76 (1H, m), 4.21-4.30 (2H, m), 4.61-4.72 (1H, m), 4.85 (4H, s), 6.99 (1H, d, J = 9.3 Hz), 7.03-7.07 (1H, m), 7.13-7.20 (2H, m), 7.77 (1H, d, J = 1.5 Hz), 7.82-7.85 (1H, m), 8.72-8.76 (1H, m) 85 CD₃OD 400 1.50 (3H, d, J = 6.96 Hz), 2.56 (3H, s), 2.96-3.01 (1H, m), 3.06-3.11 (1H, m), 3.84 (1H, q, J = 6.9 Hz), 4.15-4.28 (2H, m), 4.60 (1H, t, J = 2.0 Hz), 4.86 (4H, s), 6.95-6.98 (1H, m), 7.04-7.07 (1H, m), 7.11-7.20 (2H, m), 7.74-7.84 (2H, m), 8.56-8.68 (1H, m) 86 CD₃OD 400 1.45 (3H, s), 1.59 (3H, s), 2.55 (3H, s), 2.97-3.03 (1H, m), 3.12-3.18 (1H, m), 4.22-4.28 (2H, m), 4.62-4.68 (1H, m), 8.86 (3H, s), 6.99 (1H, d, J = 9.2 Hz), 7.05-7.07 (1H, m), 7.13-7.20 (2H, m), 7.76 (1H, d, J = 7.95 Hz), 7.81 (1H, dd, J = 2.0, 9.2 Hz), 8.31 (1H, d, J = 7.6 Hz), 8.66-8.68 (1H, m) 87 CD₃OD 400 1.12-1.16 (4H, m), 2.63 (3H, s), 2.88-2.97 (1H, m), 3.12-3.20 (1H, m), 3.87 (1H, q, J = 4.0 Hz), 4.22 (2H, s), 4.59-4.66 (1H, m), 5.01 (4H, br s), 6.95-7.01 (3H, m), 7.22-7.26 (2H, m), 7.69-7.77 (2H, m) 88 CD₃OD 400 1.49 (3H, d, J = 7.0 Hz), 2.53 (3H, s), 2.92-3.00 (1H, m), 3.05-3.19 (1H, m), 3.31-3.33 (4H, m), 3.79-3.82 (1H, m), 4.11-4.17 (1H, m), 4.23-4.28 (1H, m), 4.59-4.70 (1H, m), 6.94-7.01 (3H, m), 7.23-7.28 (2H, m), 7.68-7.71 (2H, m), 8.62-8.72 (1H, m) 90 CD₃OD 270 1.70-2.00 (2H, m), 2.05-2.20 (1H, m), 2.40-2.60 (1H, m), 2.88 (3H, s), 2.90-3.40 (4H, m), 3.60-3.70 (1H, m), 4.00-4.40 (3H, m), 4.60-4.70 (1H, m), 4.80-5.00 (2H, m), 6.90-7.00 (1H, m), 7.10-7.20 (1H, m), 7.30-7.50 (2H, m), 7.70-7.80 (2H, m), 8.70-8.80 (1H, m) 91 CD₃OD 270 1.50-1.70 (1H, m), 1.75-1.90 (1H, m), 2.00-2.20 (1H, m), 2.30-2.50 (1H, m), 2.86 (3H, s), 2.90-3.40 (5H, m), 3.55-3.70 (1H, m), 4.00-4.10 (1H, m), 4.20-4.30 (2H, m), 4.70-4.80 (1H, m), 4.90-5.10 (1H, m), 6.95 (1H, d, J = 9.15 Hz), 7.40-7.60 (4H, m), 7.70-7.80 (2H, m), 8.75-8.90 (1H, m) 92 CD₃OD 270 1.70-1.90 (2H, m), 1.95-2.20 (1H, m), 2.40-2.60 (1H, m), 2.85 (3H, s), 3.00-3.20 (1H, m), 3.30-3.33 (1H, m), 3.60-3.70 (2H, m), 4.03-4.08 (2H, m), 4.18-4.23 (1H, m), 4.82-4.93 (5H, m), 6.86 (1H, d, J = 8.9 Hz), 7.33-7.36 (2H, m), 7.48-7.57 (4H, m), 7.74-7.78 (1H, m), 7.84-7.87 (1H, m), 8.16 (1H, d, J = 7.9 Hz) 93 CD₃OD 270 1.61-1.68 (1H, m), 1.82-1.85 (1H, m), 2.03-2.11 (1H, m), 2.43 (1H, br, s) 2.88-2.95 (3H, m), 3.13-3.18 (2H, m), 3.65 (1H, br, s), 4.08 (1H, t, J = 8.2 Hz), 4.21 (2H, s), 4.65 (1H, t, J = 8.9 Hz), 4.93 (5H, s), 6.96 (1H, d, J = 9.7 Hz), 7.19-7.27 (4H, m), 7.73 (2H, d, J = 8.7 Hz) 94 CD₃OD 270 1.78-1.92 (1H, m), 2.13-2.16 (1H, m), 2.47-2.51 (1H, m), 2.88 (4H, s), 2.98-3.01 (2H, m), 3.14-3.19 (1H, m), 3.64-3.69 (1H, m), 4.23 (2H, s), 4.70 (1H, t, J = 7.4 Hz), 4.92 (5H, s), 6.96 (1H, d, J = 9.2 Hz), 7.12-7.23 (2H, m), 7.74-7.82 (2H, m) 95 CD₃OD 270 1.68-1.83 (2H, m), 2.07 (1H, s), 2.39 (1H, s), 2.86 (3H, s), 3.15-3.39 (2H, m), 4.07-4.24 (3H, m), 4.83-4.92 (7H, m), 6.85 (1H, d, J = 5.9 Hz), 7.34 (3H, s), 7.62 (2H, s), 7.85 (2H, s) 96 CD₃OD 270 3.85 (1H, s), 4.03 (1H, s), 4.59 (1H, s), 5.01 (3H, s), 5.29-5.43 (2H, m), 5.79 (1H, s), 6.81-7.03 (7H, m), 8.96-9.09 (4H, m), 9.87 (2H, s) 97 CD₃OD 270 1.8-2.0 (4H, m), 2.1-2.3 (1H, m), 2.5-2.8 (1H, m), 2.9-3.0 (3H, s), 3.0-3.3 (4H, m) 3.6-3.8 (1H, m), 4.0-4.3 (4H, m), 4.8-5.0 (1H, m) 7.0 (1H, d, J = 7 Hz), 7.8-7.9 (2H, m) 98 CD₃OD 270 1.60-2.20 (3H, m), 2.35-2.50 (1H, m), 2.87 (3H, s), 2.90-3.35 (5H, m), 3.60-3.70 (1H, m), 4.00-4.30 (3H, m), 4.60-4.70 (1H, m), 4.90-5.10 (1H, m), 6.90-7.10 (3H, m), 7.15-7.30 (2H, m), 7.70-7.80 (2H, m), 8.60-8.80 (1H, m) 99 CD₃OD 270 1.65-1.70 (1H, m), 1.86-1.88 (1H, m), 2.09-2.12 (1H, m), 2.39-2.43 (1H, m), 2.88 (3H, s), 3.14-3.19 (2H, m), 3.30 (1H, s), 3.61-3.64 (1H, m), 4.06 (1H, t J = 8.4 Hz), 4.22-4.23 (2H, m), 4.69 (1H, t, J = 6.4 Hz), 4.92 (4H, br, s), 6.94-7.06 (4H, m), 7.24-7.29 (1H, m), 7.70-7.77 (2H, m) 100 d⁶DMSO 270 1.7-1.8 (1H, m), 1.9-2.0 (1H, m), 2.2-2.4 (1H, m), 2.3-2.4 (1H, m), 2.5 (1H, s), 2.6-2.8 (4H, m), 2.9-3.2 (1H, m), 3.3-3.6 (6H, m), 3.9-4.4 (2H, m), 4.6-4.8 (1H, m), 6.8-6.9 (2H, m), 7.0-7.1 (1H, d, J = 7 Hz), 7.2-7.3 (2H, m) 7.6-7.7 (1H, d, J = 7 Hz), 7.8 (1H, s), 8.0-8.2 (1H, m), 8.8-8.9 (1H, m), 9.0-9.1 (1H, m) 101 d⁶DMSO 270 2.5 (3H, s), 3.0-3.3 (3H, m), 3.6-3.9 (3H, m), 3.7-4.0 (7H, m), 6.9-7.0 (1H, d, J = 9 Hz), 7.2-7.4 (4H, m), 7.7-7.6 (1H, d, J = 9 Hz), 7.77-7.8 (1H, s), 8.2 (1H, s), 8.6 (2H, s), 9.3 (1H, s) 102 d⁶DMSO 270 1.0-1.1 (9H, s), 1.3-1.4 (1H, m), 1.8-2.0 (1H, m), 2.1-2.2 (1H, m), 2.5-2.4 (6H, m), 2.6 (3H, s), 3.8-4.0 (1H, m), 4.1-4.2 (2H, m), 4.6-4.8 (1H, m), 6.5-6.8 (2H, m), 7.1-7.2 (2H, m), 7.3-7.35 (2H, m), 7.4-7.45 (1H, m), 7.9 (1H, s), 8.7 (1H, s), 8.9 (1H, s) 103 CD₃OD 400 1.66-1.74 (1H, m), 1.84-1.92 (1H, m), 2.08-2.18 (1H, m), 2.43-2.50 (1H, m), 2.89-2.93 (5H, m), 3.13-3.19 (2H, m), 3.65-3.69 (1H, m), 4.09 (1H, t, J = 8.0 Hz), 4.24-4.30 (2H, m), 4.70-4.72 (1H, m), 4.90 (3H, br, s), 7.01 (1H, d, J = 8.0 Hz), 7.10-7.13 (1H, m), 7.22-7.37 (3H, m), 7.72 (1H, s), 7.76-7.89 (1H, m) 104 CD₃OD 400 1.71-1.92 (2H, m), 2.09-2.15 (1H, m), 2.30 (3H, s), 2.35-2.51 (1H, m), 2.89 (3H, s), 2.92-2.98 (1H, m), 3.13-3.19 (2H, m), 3.63-3.66 (1H, m), 4.07 (1H, t, J = 8.0 Hz), 4.16-4.25 (2H, m), 4.71 (1H, t, J = 8.0 Hz), 4.91 (4H, br, s), 6.95 (1H, d, J = 12.0 Hz), 7.04-7.13 (4H, m), 7.65 (1H, s), 7.68-7.75 (1H, m) 105 CD₃OD 400 1.63-1.70 (1H, m), 1.83-1.88 (1H, m), 2.06-2.16 (1H, m), 2.27 (3H, m), 2.37-2.46 (1H, m), 2.87-2.91 (3H, m), 3.12-3.19 (2H, m), 3.31-3.32 (1H, m), 3.62-3.68 (1H, m), 4.07 (1H, t, J = 8.0 Hz), 4.21-4.30 (2H, m), 4.67-4.70 (1H, m), 4.90 (4H, br, s), 6.89-7.05 (3H, m), 7.10-7.20 (1H, m), 7.64-7.79 (2H, m), 8.71-8.76 (1H, m) 106 CD₃OD 400 1.64-1.73 (1H, m), 1.82-1.89 (1H, m), 2.04-2.15 (1H, m), 2.29 (3H, s), 2.37-2.47 (1H, m), 2.85-2.91 (4H, m), 3.10-3.19 (2H, m), 3.63-3.69 (1H, m), 4.08 (1H,, t J = 8.0 Hz), 4.18-4.27 (2H, m), 4.65-4.67 (1H, m), 4.90 (4H, br, s), 6.89-6.94 (1H, m), 7.06-7.30 (4H, m, 7.65-7.74 (2H, m) 107 CD₃OD 400 1.67-1.76 (1H, m), 1.82-1.93 (1H, m), 2.07-2.17 (1H, m), 2.41-2.49 (1H, m), 2.86-2.89 (4H, m), 3.07-3.20 (2H, m), 3.64-3.68 (1H, m), 3.69-3.75 (3H, m), 4.09 (1H, t, J = 8.0 Hz), 4.18-4.29 (2H, m), 4.61-4.65 (1H, m), 4.92 (4H, br, s), 6.81 (2H, d, J = 8.0 Hz), 6.94-6.96 (1H, m), 7.13 (2H, d, J = 8.0 Hz), 7.71-7.77 (2H, m) 108 CD₃OD 400 1.70-1.76 (1H, m), 1.83-1.90 (1H, m), 2.09-2.16 (1H, m), 2.40-2.48 (1H, m), 2.88 (3H, s), 2.98-3.03 (1H, m), 3.13-3.25 (2H, m), 3.63-3.68 (1H, m), 4.08 (1H, t, J = 8.0 Hz), 4.24-4.29 (2H, m), 4.74-4.82 (1H, m), 4.92 (4H, br, s), 7.03-7.08 (1H, m), 7.10-7.19 (2H, m), 7.23-7.33 (2H, m), 7.70-7.71 (1H, m), 7.77-7.84 (1H, m) 109 CD₃OD 400 1.69-1.78 (1H, m), 1.81-1.92 (1H, m), 2.04-2.17 (1H, m), 2.42-2.51 (1H, m), 2.89 (3H, s), 3.05-3.20 (2H, m), 3.32-3.37 (1H, m), 3.62-3.68 (1H, m), 4.10 (1H, t, J = 8.0 Hz), 4.23-4.36 (2H, m), 4.82-4.85 (5H, m), 6.97 (1H, d, J = 12.0 Hz), 7.19-7.29 (3H, m), 7.32-7.40 (1H, m), 7.71 (1H, s), 7.79 (1H, dd, J = 8.0, 4.0 Hz) 110 CD₃OD 400 1.76-1.83 (1H, m), 1.87-1.94 (1H, m), 2.11-2.19 (1H, m), 2.46-2.55 (1H, m), 2.89 (3H, s), 3.04-3.08 (1H, m), 3.10-3.19 (1H, m), 3.27-3.33 (1H, m), 3.64-3.70 (1H, m), 4.10 (1H, t, J = 8.0 Hz), 4.19-4.27 (2H, m), 4.81 (1H, t, J = 8.0 Hz), 4.91 (4H, br s), 6.98 (1H, d, J = 12.0 Hz), 7.18-7.28 (2H, m), 7.43 (1H, s), 7.71-7.73 (1H, m), 7.77-7.80 (1H, m) 111 CD₃OD 400 1.74-1.81 (1H, m), 1.88-1.94 (1H, m), 2.11-2.18 (1H, m), 2.45-2.52 (1H, m), 2.89 (4H, s), 3.11-3.21 (2H, m), 3.33-3.42 (1H, m), 3.64-3.70 (1H, m), 4.11-4.30 (5H, m), 4.77 (2H, t, J = 8.0 Hz), 6.97 (1H, d, J = 8.0 Hz), 7.40-7.48 (2H, m), 7.51-7.61 (1H, m), 7.66-7.71 (2H, m), 7.78-7.83 (1H, m) 112 CD₃OD 400 1.11 (2H, t, J = 4.0 Hz), 1.74-1.87 (1H, m), 1.90-1.95 (2H, m), 2.46-2.49 (1H, m), 2.88-2.90 (5H, m), 3.11-3.18 (3H, m), 3.22-3.30 (3H, m), 3.50-3.55 (1H, m), 3.65-3.69 (1H, m), 4.11-4.16 (1H, m), 4.22-4.37 (2H, m), 6.99 (2H, d, J = 8.0 Hz), 7.77 (1H, s), 7.87 (1H, dd, J = 8.0, 4.0 Hz), 7.93-8.01 (2H, m), 8.75-8.77 (2H, br, s), 8.87 (1H, t, J = 4.0 Hz) 113 CD₃OD 400 1.54-1.59 (1H, m) 1.64-1.74 (1H, m) 1.92-1.99 (1H, m) 2.25-2.30 (1H, M) 2.72-2.76 (4H, m) 3.01-3.07 (3H, m) 3.18-3.23 (2H, m) 3.49-3.55 (1H, m) 3.94-4.12 (5H, m) 4.62 (1H, t, J = 4.0 Hz) 6.67 (1H, d, J = 8.0 Hz) 6.81-6.94 (1H, m) 6.99-7.07 (2H, m) 7.23 (1H, d, J = 8.0 Hz) 7.36-7.53 (3H, m) 114 CD₃OD 400 1.69-1.80 (2H, m), 2.04-2.11 (1H, m), 2.43-2.48 (1H, m), 2.88 (3H, s), 3.11-3.18 (1H, m), 3.31-3.33 (1H, m), 3.46-3.51 (1H, m), 3.57-3.60 (1H, m), 4.13 (1H, t, J = 8.0 Hz), 4.22-4.31 (2H, m), 4.92 (4H, br s), 5.11 (1H, t, J = 8.0 Hz), 6.85 (1H, d, J = 8.0 Hz), 7.71-7.81 (4H, m), 7.94 (1H, m), 8.07-8.19 (2H, m), 8.60-8.64 (1H, m) 115 CD₃OD 270 0.9-1.0 (3H, m), 1.1-1.4 (5H, m), 1.5-1.8 (8H, m), 2.0-2.3 (3H, m) 2.6-2.7 (1H, m) 2.9 (3H, s), 3.1-3.3 (1H, m), 3.7-3.8 (1H, m) 4.0-4.5 (4H, m), 7.0-7.1 (1H, d, J = 7 Hz), 7.7-7.8 (2H, s) 7.9-8.0 (1H, m) 116 CD₃OD 400 1.90-2.25 (3H, m), 2.50-2.65 (1H, m), 2.82 (3H, m), 2.90-3.25 (3H, m), 3.30-3.40 (2H, m), 3.65-3.80 (1H, m), 4.00-4.30 (3H, m), 4.55-4.70 (1H, m), 4.85-5.00 (1H, m), 6.90-7.25 (4H, m), 7.65-7.80 (2H, m), 8.65-8.80 (1H, m) 117 CD₃OD 270 1.24-1.29 (7H, m), 1.76-1.83 (2H, m), 2.00-2.05 (1H, m), 2.40 (1H, br, s), 2.89-2.94 (1H, m), 3.08-3.15 (2H, m), 3.49-3.64 (2H, m), 4.20-4.27 (3H, m), 4.63 (1H, t, J = 8.6 Hz), 4.98 (3H, br, s), 6.95 (1H, d, J = 9.9 Hz), 7.16 (1H, d, J = 6.6 Hz), 7.38-7.41 (2H, m), 7.72-7.75 (2H, m) 118 CD₃OD 270 1.20-1.35 (6H, m), 1.60-1.80 (2H, m), 1.90-2.10 (1H, m), 2.20-2.40 (1H, m), 3.15-3.70 (8H, m), 4.00-4.30 (3H, m), 4.75-4.95 (1H, m), 6.86 (1H, d, J = 9.40 Hz), 7.30-7.90 (8H, m), 8.15-8.20 (1H, m), 8.55-8.70 (1H, m) 119 CD₃OD 270 1.20-1.30 (6H, m), 1.75-1.85 (2H, m), 2.03-2.15 (2H, m), 2.25-2.50 (1H, m), 2.88-2.96 (2H, m), 3.07-3.14 (2H, m), 3.49-3.70 (2H, m), 4.17-4.22 (3H, m), 4.61-4.65 (1H, m), 4.90-5.10 (1H, m), 6.92-7.02 (3H, m), 7.20-7.25 (2H, m), 7.70-7.74 (2H, m), 8.65-8.80 (1H, m) 120 CD₃OD 400 1.26-1.30 (6H, m), 1.72-1.84 (2H, m), 2.00-2.09 (1H, m), 2.33-2.41 (1H, m), 2.92-2.98 (1H, m), 3.14-3.27 (2H, m), 3.50-3.63 (2H, m), 4.23-4.36 (3H, m), 4.67 (1H, t, J = 8.0 Hz), 4.93 (4H, br, s), 6.75 (1H, d, J = 8.0 Hz), 7.18-7.35 (4H, m), 7.71-7.78 (2H, m) 121 CD₃OD 400 1.26-1.30 (6H, m), 1.74-1.83 (2H, m), 2.00-2.08 (1H, m), 2.36-2.40 (3H, m), 2.95-3.00 (1H, m), 3.15-3.26 (2H, m), 3.50-3.64 (2H, m), 4.14-4.25 (3H, m), 4.68 (1h, t, J = 8.0 Hz), 4.91 (5H, br, s), 6.72 (1H, d, J = 8.0 Hz), 7.04-7.16 (4H, m), 7.64-7.79 (2H, m) 122 CD₃OD 400 1.14-1.19 (6H, m), 1.57-1.69 (2H, m), 1.89-1.94 (1H, m), 2.18 (3H, s), 2.76-2.82 (1H, m), 2.99-3.12 (2H, m), 4.11-4.13 (3H, m), 4.53-4.57 (1H, m), 4.92 (6H, br, s) 6.84 (1H, d, J = 8.0 Hz), 6.90-6.95 (3H, m), 6.99-7.08 (1H, m), 7.57-7.62 (2H, m), 8.75 (1H, d, J = 8.0 Hz) 123 CD₃OD 400 1.11-1.30 (6H, m), 1.71-1.79 (2H, m), 2.01-2.05 (1H, m), 2.28 (3H, s), 2.87-2.93 (1H, m), 3.08-3.13 (1H, m), 3.19-3.25 (1H, m), 3.31-3.32 (1H, m), 3.50-3.65 (2H, m), 4.14-4.35 (3H, m), 4.63 (1H, t, J = 8.0 Hz), 4.96 (4H, br, s), 6.95 (1H, d, J = 8.0 Hz), 7.05-7.11 (4H, m), 7.71-7.75 (2H, m) 124 CD₃OD 400 1.26-1.30 (6H, m), 1.73-1.84 (1H, m), 2.00-2.08 (1H, m), 2.34-2.39 (1H, m), 2.86-2.91 (1H, m), 3.05-3.10 (1H, m), 3.19-3.26 (1H, m), 3.50-3.63 (2H, m), 3.75 (3H, s), 4.20-4.26 (3H, m), 4.60 (1H, t, J = 8.0 Hz), 4.94 (4H, br, s), 6.80-6.82 (2H, m), 6.94 (1H, dd, J = 8.0, 4.0 Hz), 7.13 (2H, d, J = 8.0 Hz), 7.70-7.72 (2H, m) 125 CD₃OD 400 1.25-1.30 (6H, m), 1.73-1.84 (2H, m), 2.01-2.09 (1H, m), 2.34-2.43 (1H, m), 3.00-3.06 (1H, m), 3.19-3.26 (2H, m), 3.50-3.62 (2H, m), 4.22-4.36 (3H, m), 4.71-4.76 (1H, m), 4.98 (4H, br, s), 7.01 (1H, d, J = 8.0 Hz), 7.04-7.09 (2H, m), 7.23-7.36 (2H, m), 7.70 (1H, s), 7.77 (1H, dd, J = 8.0, 4.0 Hz) 126 CD₃OD 400 1.26-1.30 (6H, m), 1.76-1.84 (2H, m), 2.01-2.10 (1H, m), 2.37-2.42 (1H, m), 3.09-3.14 (1H, m), 3.20-3.33 (2H, m), 3.50-3.63 (2H, m), 4.21-4.32 (3H, m), 4.80 (1H, t, J = 8.0 Hz), 4.88 (4H, br, s) 6.96 (1H, d, J = 8.0 Hz), 7.16-7.28 (2H, m), 7.37-7.47 (1H, m), 7.70 (1H, s) 7.75-7.83 (1H, m), 8.69 (1H, t, J = 8.0 Hz) 127 CD₃OD 400 1.07-1.17 (6H, m), 1.66-1.73 (2H, m), 1.93-2.00 (1H, m), 2.30-2.35 (1H, m), 2.96-3.04 (1H, m), 3.14-3.21 (2H, m), 3.40-3.52 (2H, m), 4.04-4.24 (3H, m), 4.65 (1H, t, J = 8.0 Hz), 4.88 (4H, br, s), 6.90 (1H, d, J = 12.0 Hz), 7.05-7.18 (2H, m), 7.31 (1H, s), 7.62-7.73 (2H, m) 128 CD₃OD 400 1.25-1.30 (6H, m), 1.76-1.89 (2H, m), 2.04-2.11 (1H, m), 2.37-2.44 (1H, m), 3.14-3.26 (2H, m), 3.31-3.38 (1H, m), 3.50-3.65 (2H, m), 4.15-4.37 (3H, m), 4.75 (1H, t, J = 8.0 Hz), 4.99 (4H, br, s), 6.96 (1H, d, J = 8.0 Hz), 7.40-7.46 (2H, m), 7.51-7.55 (1H, m), 7.67-7.71 (2H, m), 7.78 (1H, dd, J = 8.0, 4.0 Hz) 129 CD₃OD 400 1.26-1.30 (5H, m), 1.78-1.87 (1H, m), 2.04-2.09 (1H, m), 2.39-2.44 (1H, m), 3.24-3.33 (3H, m), 3.44-3.63 (3H, m), 4.24-4.35 (3H, m), 4.82-4.89 (7H, m), 6.99 (1H, d, J = 12.0 Hz), 7.77 (1H, s), 7.84-7.89 (2H, m) 130 CD₃OD 400 1.22-1.26 (6H, m), 1.67-1.75 (2H, m), 1.92-2.01 (1H, m), 2.26-2.32 (1H, m), 3.11-3.17 (2H, m), 3.30-3.33 (1H, m), 3.44-3.58 (2H, m), 4.09-4.14 (2H, m), 4.17-4.24 (1H, m), 4.71 (1H, t, J = 8.0 Hz), 4.93 (5H, br s), 6.85 (1H, d, J = 12.0 Hz), 6.92-7.01 (1H, m), 7.07-7.13 (2H, m), 7.34 (1H, d, J = 8.0 Hz), 7.47-7.61 (3H, m) 131 CD₃OD 400 1.27 (3H, t, J = 7.3 Hz), 1.72-1.81 (1H, m), 1.85-1.96 (1H, m), 2.06-2.19 (1H, m), 2.42-2.49 (1H, m), 2.89-2.96 (2H, m), 3.09-3.29 (4H, m), 3.65-3.73 (1H, m), 4.10 (1H, t, J = 8.4 Hz), 4.16 (1H, d, J = 15.1 Hz), 4.31 (1H, d, J = 15.1 Hz), 4.65 (1H, dd, J = 7.0, 8.7 Hz), 4.86 (2H, s), 6.96 (1H, d, J = 9.1 Hz), 7.01-7.04 (1H, m), 7.10-7.24 (2H, m), 7.74-7.78 (2H, m), 8.65-8.75 (1H, m) 132 CD₃OD 400 0.95 (3H, t, J = 7.3 Hz), 1.55-1.61 (3H, m), 1.62-1.68 (1H, m), 1.70-1.87 (1H, m), 2.00-2.12 (1H, m), 2.34-2.44 (1H, m), 2.89-3.33 (6H, m), 3.58-3.71 (2H, m), 3.97 (1H, dd, J = 7.2, 9.0 Hz), 4.21 (2H, s), 4.64 (1H, dd, J = 6.4, 9.0 Hz), 4.86 (1H, s), 6.72 (1H, d, J = 8.7 Hz), 7.00-7.04 (1H, m), 7.12-7.19 (2H, m), 7.54 (1H, dd, J = 2.2, 8.9 Hz), 7.80 (1H, d, J = 1.7 Hz) 133 CD₃OD 400 0.97 (3H, d, J = 6.6 Hz), 1.03 (3H, d, J = 6.6 Hz), 1.71-1.79 (1H, m), 1.90-2.04 (2H, m), 2.07-2.23 (1H, m), 2.39-2.48 (1H, m), 2.85-3.04 (4H, m), 3.11-3.21 (2H, m), 3.74-3.79 (1H, m), 4.13 (1H, t, J = 8.5 Hz), 4.18-4.34 (2H, m), 4.65 (1H, dd, J = 6.7, 8.85 Hz), 4.87 (2H, s), 6.97 (1H, d, J = 9.4 Hz), 7.01-7.05 (1H, m), 7.11-7.20 (2H, m), 7.76 (1H, d, J = 10.1 Hz), 7.78-7.81 (1H, m), 8.73-8.76 (1H, m) 135 CD₃OD 400 1.70-1.80 (1H, m), 1.81-2.00 (1H, m), 2.05-2.20 (1H, m), 2.30-2.50 (1H, m), 2.80-2.95 (1H, m), 3.10-3.40 (6H, m), 3.70-3.85 (1H, m), 3.95-4.00 (1H, m), 4.05-4.15 (1H, m), 4.20-4.50 (3H, m), 4.60-4.70 (1H, m), 6.90-7.10 (1H, m), 7.11-7.30 (1H, m), 7.65-7.75 (1H, m), 7.80-7.90 (1H, m), 8.65-8.80 (1H, m) 136 CD₃OD 400 1.27 (3H, t, J = 7.2 Hz), 1.71-1.80 (1H, m), 1.83-1.94 (1H, m), 2.07-2.17 (1H, m), 2.37-2.44 (1H, m), 2.89-2.98 (2H, m), 3.07-3.32 (6H, m), 3.66-3.72 (1H, m), 4.09 (1H, t, J = 8.4 Hz), 4.15-4.36 (2H, m), 4.63-4.67 (1H, m), 6.95-7.09 (3H, m), 7.22-7.30 (2H, m), 7.72-7.86 (2H, m), 8.69-8.72 (1H, m) 137 CD₃OD 400 1.25-1.28 (3H, m), 1.66-1.70 (1H, m), 1.82-1.87 (1H, m), 2.04-2.12 (1H, m), 2.29 (3H, s), 2.36-2.41 (1H, m), 2.86-2.92 (1H, m), 3.10-3.27 (5H, m), 3.31-3.33 (1H, m), 3.65-3.71 (1H, m), 4.10 (1H, t, J = 8.0 Hz), 4.18-4.28 (2H, m), 4.65-4.69 (1H, m), 4.87 (2H, br, s), 6.88 (1H, d, J = 12.0 Hz), 6.96-7.06 (3H, m), 7.10-7.17 (1H, m), 7.61-7.73 (2H, m) 138 CD₃OD 400 1.25-1.28 (3H, m), 1.69-1.74 (1H, m), 1.83-1.97 (1H, m), 2.08-2.14 (1H, m), 2.40-2.45 (1H, m), 2.91-2.96 (1H, m), 3.11-3.33 (5H, m), 3.616-3.72 (1H, m), 4.12 (1H, t, J = 8.0 Hz), 4.19-4.28 (2H, m), 4.69 (1H, t, J = 4.0 Hz), 4.89 (3H, br, s), 6.97 (1H, d, J = 8.0 Hz), 7.17-7.19 (1H, m), 7.22-7.29 (3H, m), 7.72 (1H, s), 7.77 (1H, dd, J = 8.0, 4.0 Hz) 139 CD₃OD 400 0.97 (3H, t, J = 7.4 Hz), 1.65-1.77 (4H, m), 1.85-1.92 (1H, m), 2.07-2.15 (1H, m), 2.37-2.44 (1H, m), 2.90-2.96 (2H, m), 3.03-3.20 (4H, m), 3.68-3.73 (1H, m), 4.10 (1H, t, J = 8.2 Hz), 4.20-4.29 (2H, m), 4.65 (1H, dd, J = 6.98, 8.61 Hz), 4.86 (1H, s), 6.95-7.02 (3H, m), 7.22-7.25 (2H, m), 7.72-7.76 (2H, m), 8.69-8.72 (1H, m) 140 CD₃OD 400 1.65-1.70 (1H, m), 1.85-2.00 (1H, m), 2.10-2.25 (1H, m), 2.35-2.50 (1H, m), 2.80-2.90 (1H, m), 3.00-3.10 (1H, m), 3.25-3.40 (4H, m), 3.45-3.60 (1H, m), 4.10-4.40 (5H, m), 4.50-4.60 (1H, m), 6.90-7.00 (1H, m), 7.05-7.20 (2H, m), 7.40-7.65 (5H, m), 7.70-7.80 (2H, m), 8.60-8.80 (1H, m) 141 CD₃OD 270 1.69-2.03 (4H, m), 2.89-2.94 (1H, m), 3.12-3.32 (4H, m), 4.17-4.28 (5H, m), 4.30-4.35 (1H, m), 4.96 (3H, br, s), 6.95 (1H, d, J = 8.9 Hz), 7.15-7.19 (2H, m), 7.33-7.42 (6H, m), 7.73-7.76 (2H, m) 143 CD₃OD 400 1.71-1.76 (1H, m), 1.89-1.98 (1H, m), 2.12-2.18 (1H, m), 2.43-2.50 (1H, m), 2.84-2.90 (1H, m), 3.02-3.07 (1H, m), 3.31-3.33 (1H, m), 3.52-3.57 (1H, m), 4.11-4.18 (2H, m), 4.27-4.38 (3H, m), 4.56 (1H, dd, J = 7.2, 8.3 Hz), 4.86 (3H, s), 6.96-6.99 (2H, m), 7.05-7.17 (2H, m), 7.39-7.48 (3H, m), 7.53 (1H, s), 7.75-7.77 (2H, m), 8.63-8.66 (1H, m) 144 CD₃OD 400 1.50-2.00 (6H, m), 2.78 (3H, s), 2.85-2.95 (1H, m), 3.05-3.15 (2H, m), 3.25-3.35 (2H, m), 3.40-3.50 (1H, m), 3.55-3.70 (1H, m), 4.10-4.30 (2H, m), 4.50-4.60 (1H, m), 4.80-5.00 (1H, m), 6.90-7.20 (4H, m), 7.65-7.80 (2H, m), 8.70-8.80 (1H, m) 145 CD₃OD 400 1.52-1.63 (2H, m), 1.72-1.93 (4H, m), 2.78 (3H, s), 2.86-2.97 (2H, m), 3.08-3.14 (2H, m), 3.46-3.54 (1H, m), 3.65-3.69 (1H, m), 4.16 (1H, d, J = 15.1 Hz), 4.25 (1H, d, J = 15.1 Hz), 4.59 (1H, dd, J = 7.3, 8.4 Hz), 4.86 (3H, s), 6.92-7.02 (3H, m), 7.21-7.24 (2H, m), 7.69-7.71 (2H, m) 146 CD₃OD 400 1.32 (6H, dd, J = 6.66, 25.1), 1.56-1.61 (1H, m), 1.68-1.97 (4H, m), 2.90-2.98 (2H, m), 3.00-3.14 (1H, m), 3.44 (1H, d, J = 13.05 Hz), 3.54-3.74 (2H, m), 3.94-3.97 (1H, m), 4.14-4.30 (2H, m), 4.55-4.61 (1H, m), 4.86 (2H, m), 6.98 (1H, d, J = 9.2 Hz), 7.06-7.12 (1H, m), 7.13-7.21 (2H, m), 7.76-7.81 (2H, m), 8.69-8.72 (1H, m), 8.86-8.92 (1H, m) 147 CD₃OD 270 1.25-1.40 (6H, m), 1.44-1.92 (5H, m), 2.80-2.97 (2H, m), 3.30-3.36 (2H, m), 3.74-3.90 (2H, m), 4.11-4.28 (2H, m), 4.55-4.60 (1H, m), 4.90 (5H, br, s), 6.92-7.00 (2H, m), 7.19-7.24 (2H, m), 7.66-7.69 (2H, m), 8.67-8.69 (1H, m) 148 CD₃OD 400 1.82-1.88 (1H, m), 2.62-2.79 (1H, m), 2.91 (3H, s), 2.94-3.00 (1H, m), 3.08-3.18 (1H, m), 3.28-3.32 (1H, m), 3.57 (1H, d, J = 11.6 Hz), 4.07-4.34 (3H, m), 4.49 (1H, s, br), 4.62-4.69 (1H, m), 4.92 (3H, s), 6.96 (1H, d, J = 9.1 Hz), 7.00-7.03 (1H, m), 7.11-7.24 (2H, m), 7.73-7.81 (2H, m), 8.69-8.11 (1H, m) 149 CD₃OD 400 2.87-2.98 (1H, m), 3.00 (3H, s), 3.04-3.15 (2H, m), 3.20-3.26 (1H, m), 4.16-4.18 (2H, m), 4.20-4.34 (1H, m), 4.43 (1H, d, J = 15.4 Hz), 4.57 (1H, d, J = 15.5 Hz), 4.65 (1H, dd, J = 7.05, 8.61 Hz), 4.86 (4H, s), 6.97 (1H, d, J = 9.1 Hz), 7.04-7.07 (1H, m), 7.12-7.36 (4H, m), 7.74-7.79 (2H, m), 8.72-8.75 (2H, m) 150 CD₃OD 270 1.28-1.30 (6H, m), 2.75 (3H, s), 2.89-2.97 (2H, m), 3.07-3.30 (2H, m), 3.40-3.45 (1H, m), 3.83-3.95 (2H, m), 4.12-4.27 (2H, m), 4.65 (1H, t, J = 6.9 Hz), 4.95 (2H, br, s), 6.93-6.96 (1H, m), 7.17 (1H, dd, J = 8.2, 1.5 Hz), 7.40 (2H, d, J = 8.2 Hz), 7.71 (2H, br, s) 151 CD₃OD 270 1.25-1.50 (9H, m), 2.59 (3H, s), 2.85-3.15 (2H, m), 3.25-3.35 (2H, m), 3.75-3.95 (2H, m), 4.05-4.35 (2H, m), 4.55-4.70 (1H, m), 4.90-5.10 (2H, m), 6.85-6.95 (1H, m), 7.10-7.20 (1H, m), 7.35-7.45 (2H, m), 7.60-7.75 (2H, m) 152 CD₃OD 270 2.79 (3H, s), 2.85-3.30 (3H, m), 3.80-3.95 (2H, m), 4.10-4.30 (4H, m), 4.60-4.70 (1H, m), 4.90-5.10 (1H, m), 6.90-7.00 (1H, m), 7.10-7.20 (1H, m), 7.30-7.50 (8H, m), 7.60-7.80 (2H, m), 8.60-8.80 (1H, m) 153 CD₃OD 270 2.86 (6H, s), 2.90-310 (2H, m), 3.25-3.40 (2H, m), 3.85-4.30 (2H, m), 4.55-4.70 (1H, m), 4.80-5.00 (1H, m), 6.90-7.00 (1H, m), 7.10-7.20 (1H, m), 7.30-7.50 (2H, m), 7.60-7.80 (2H, m), 8.65-8.80 (1H, m) 154 CD₃OD 270 0.98 (6H, d, J = 6.43 Hz), 1.95-2.15 (1H, m), 2.70-3.15 (7H, m), 3.25-3.40 (1H, m), 3.80-4.05 (2H, m), 4.10-4.35 (2H, m), 4.60-4.70 (1H, m), 4.90-5.20 (2H, m), 6.90-7.00 (1H, m), 7.10-7.20 (1H, m), 7.35-7.50 (2H, m), 7.65-7.80 (2H, m), 8.70-8.80 (1H, m) 155 CD₃OD 270 0.75-0.90 (7H, m), 1.25-1.40 (7H, m), 1.60-1.80 (1H, m), 2.60 (3H, s), 2.65-3.05 (5H, m), 3.60-3.95 (2H, m), 4.10-4.40 (2H, m), 4.60-4.70 (1H, m), 6.90-7.10 (1H, m), 7.15-7.25 (1H, m), 7.40-7.50 (2H, m), 7.60-7.80 (2H, m), 8.70-8.90 (1H, m) 156 CD₃OD 270 1.20-1.40 (6H, m), 2.75 (3H, s), 2.85-3.15 (2H, m), 3.25-3.35 (1H, m), 3.40-4.00 (1H, m), 4.10-4.30 (2H, m), 4.55-4.70 (1H, m), 4.80-5.10 (4H, m), 6.90-7.40 (4H, m) 7.65-7.90 (2H, m), 8.70-8.80 (1H, m) 157 CD₃OD 400 1.16 (3H, d, J = 6.1 Hz), 1.27 (6H, d, J = 6.5 Hz), 1.34 (3H, d, J = 6.1 Hz), 2.90-3.16 (2H, m), 3.65-3.73 (2H, m), 3.81-3.97 (2H, m), 4.17-4.28 (2H, m), 4.59-4.69 (1H, m), 6.95-6.98 (1H, m), 7.0-7.05 (1H, m), 7.12-7.19 (2H, m), 7.73-7.79 (2H, m), 8.73-8.76 (1H, m). 158 CD₃OD 400 0.95 (6H, t, J = 7.3 Hz), 1.65 (4H, br s), 2.89-2.95 (1H, m), 3.03-3.16 (6H, m), 3.88-4.03 (2H, m), 4.22-4.24 (2H, m), 4.63-4.67 (1H, m), 6.97 (1H, d, J = 9.2 Hz), 7.03-7.06 (1H, m), 7.12-7.19 (2H, m), 7.73 (1H, d, J = 1.2 Hz), 7.78 (1H, dd, J = 9.2, 2.1 Hz), 8.74 (1H, t, J = 5.9 Hz). 159 CD₃OD 400 1.00 (12H, dd, J = 6.6, 3.0 Hz), 2.00-2.04 (2H, m), 2.89-3.18 (6H, m), 3.96-4.12 (2H, m), 4.24-4.25 (2H, m), 4.66-4.71 (1H, m), 6.97 (1H, d, J = 9.1 Hz), 7.04-7.07 (1H, m), 7.12-7.19 (2H, m), 7.74 (1H, d, J = 1.3 Hz), 7.79 (1H, dd, J = 9.2, 2.1 Hz). 160 CD₃OD 400 2.91-3.10 (4H, m), 3.21-3.33 (3H, m), 3.78-3.89 (2H, m), 4.12-4.28 (2H, m), 4.60 (1H, s, J = 7.6 Hz), 6.95 (1H, d, J = 9.1 Hz), 7.00-7.03 (1H, m), 7.09-7.16 (2H, m), 7.25-7.37 (5H, m), 7.71-7.75 (2H, m), 8.69 (1H, t, J = 5.8 Hz). 161 CD₃OD 400 2.92-3.13 (7H, m), 3.32-3.38 (2H, m), 3.98-4.09 (2H, m), 4.17-4.27 (2H, m), 4.61-4.65 (1H, m), 6.95 (1H, d, J = 9.1 Hz), 7.01-7.04 (1H, m), 7.08-7.17 (2H, m), 7.24-7.35 (5H, m), 7.72 (1H, s), 7.75 (1H, dd, J = 9.2, 2.0 Hz), 8.73 (1H, t, J = 5.8 Hz). 162 CD₃OD 400 2.86-2.95 (4H, m), 3.01-3.14 (1H, m), 3.87-4.04 (4H, m), 4.14-4.24 (2H, m), 4.58-4.66 (1H, m), 6.24-6.31 (1H, m), 6.87-7.03 (3H, m), 7.07-7.50 (7H, m), 7.71-7.77 (2H, m), 8.69-8.84 (1H, m). 163 CD₃OD 400 2.83 (3H, s), 2.89-2.95 (1H, m), 3.02-3.11 (1H, m), 3.89-3.99 (2H, m), 4.15-4.30 (4H, m), 4.59-4.63 (1H, m), 6.95 (1H, d, J = 9.0 Hz), 7.00-7.04 (1H, m), 7.10-7.17 (2H, m), 7.46-7.51 (4H, m), 7.72 (1H, d, J = 1.3 Hz), 7.76 (1H, dd, J = 9.1, 2.1 Hz), 8.72 (1H, t, J = 5.9 Hz). 164 CD₃OD 400 2.84 (3H, s), 2.90-2.95 (1H, m), 3.02-3.12 (1H, m), 3.90-4.01 (2H, m), 4.16-4.34 (4H, m), 4.60-4.64 (1H, m), 6.95 (1H, d, J = 9.1 Hz), 7.00-7.04 (1H, m), 7.10-7.17 (2H, m), 7.42-7.57 (4H, m), 7.72 (1H, d, J = 1.1 Hz), 7.76 (1H, dd, J = 9.1, 2.0 Hz), 8.72 (1H, t, J = 5.8 Hz). 165 CD₃OD 400 2.87 (3H, s), 2.90-2.95 (1H, m), 3.02-3.12 (1H, m), 3.97-4.08 (2H, m), 4.19-4.27 (2H, m), 4.43-4.54 (2H, m), 4.60-4.64 (1H, m), 6.95 (1H, d, J = 9.2 Hz), 7.01-7.04 (1H, m), 7.10-7.17 (2H, m), 7.42-7.63 (4H, m), 7.72 (1H, s), 7.76 (1H, dd, J = 9.1, 2.1 Hz), 8.72 (1H, t, J = 5.8 Hz). 166 CD₃OD 400 2.81 (3H, s), 2.89-2.94 (1H, m), 3.06-3.11 (1H, m), 3.84 (3H, s), 3.87-3.94 (2H, m), 4.15-4.27 (4H, m), 4.59-4.63 (1H, m), 6.95 (1H, d, J = 9.0 Hz), 6.99-7.03 (3H, m), 7.10-7.17 (2H, m), 7.38 (2H, d, J = 8.7 Hz), 7.72 (1H, d, J = 1.3 Hz), 7.75 (1H, dd, J = 9.1, 2.1 Hz), 8.71 (1H, t, J = 5.8 Hz). 167 CD₃OD 400 1.55-1.85 (6H, m), 2.91-3.12 (4H, m), 3.35-3.45 (2H, m), 3.83-3.94 (2H, m), 4.16-4.30 (2H, m), 4.60-4.65 (1H, s), 6.96 (1H, d, J = 9.4 Hz), 7.01-7.04 (1H, m), 7.10-7.19 (2H, m), 7.72 (1H, d, J = 1.2 Hz), 7.76 (1H, dd, J = 9.2, 2.1 Hz), 8.71 (1H, t, J = 5.8 Hz). 168 CD₃OD 400 2.87 (3H, s), 2.90-2.95 (1H, m), 3.02-3.12 (1H, m), 3.97-4.08 (2H, m), 4.19-4.27 (2H, m), 4.43-4.54 (2H, m), 4.60-4.64 (1H, m), 6.95 (1H, d, J = 9.2 Hz), 7.01-7.04 (1H, m), 7.10-7.17 (2H, m), 7.42-7.63 (4H, m), 7.72 (1H, s), 7.76 (1H, dd, J = 9.1, 2.1 Hz), 8.72 (1H, t, J = 5.8 Hz). 169 CD₃OD 400 0.94-1.02 (2H, m), 1.16-1.37 (3H, m), 1.68-1.77 (6H, m), 2.88 (3H, s), 2.92-2.95 (3H, m), 3.10-3.15 (1H, m), 3.87-4.00 (2H, m), 4.18-4.28 (2H, m), 4.64 (1H, t, J = 7.6 Hz), 6.96 (1H, d, J = 9.1 Hz), 7.02-7.05 (1H, m), 7.12-7.19 (2H, m), 7.73 (1H, s), 7.78 (1H, dd, J = 9.1, 2.0 Hz), 8.73 (1H, t, J = 5.8 Hz). 170 CD₃OD 400 1.55-1.85 (6H, m), 2.91-3.12 (4H, m), 3.35-3.45 (2H, m), 3.83-3.94 (2H, m), 4.16-4.30 (2H, m), 4.60-4.65 (1H, s), 6.96 (1H, d, J = 9.4 Hz), 7.01-7.04 (1H, m), 7.10-7.19 (2H, m), 7.72 (1H, d, J = 1.2 Hz), 7.76 (1H, dd, J = 9.2, 2.1 Hz), 8.71 (1H, t, J = 5.8 Hz) 171 CD₃OD 400 2.92-2.97 (1H, m), 3.07-3.14 (1H, m), 3.31-3.32 (4H, m), 3.92-4.04 (6H, m), 4.17-4.26 (2H, m), 4.59-4.65 (1H, m), 6.96 (1H, d, J = 9.2 Hz), 7.01-7.04 (1H, m), 7.10-7.17 (2H, m), 7.72 (1H, s), 7.76 (1H, dd, J = 9.1, 2.0 Hz), 8.73 (1H, t, J = 5.9 Hz). 172 CD₃OD 400 2.93-2.99 (1H, m), 3.10-3.21 (3H, m), 3.56 (2H, t, J = 6.0 Hz), 4.05-4.28 (4H, m), 4.45 (2H, s), 4.64-4.69 (1H, m), 6.97 (1H, d, J = 9.1 Hz), 7.03-7.06 (1H, m), 7.13-7.20 (3H, m), 7.26-7.34 (3H, m), 7.73 (1H, d, J = 1.2 Hz), 7.78 (1H, dd, J = 9.2, 2.0 Hz), 8.76 (1H, t, J = 5.9 Hz). 173 CD₃OD 400 1.85-1.94 (2H, m), 2.67 (2H, t, J = 6.3 Hz), 2.82-2.99 (2H, m), 3.13-3.25 (2H, m), 3.66-3.76 (2H, m), 4.09-4.13 (2H, m), 4.48-4.53 (1H, m), 6.09-6.12 (1H, m), 6.49-6.52 (1H, m), 6.77-6.97 (6H, m), 7.60 (1H, d, J = 1.4 Hz), 7.66 (1H, dd, J = 9.2, 2.1 Hz), 8.52 (1H, t, J = 5.8 Hz). 174 CD₃OD 400 2.89-2.96 (1H, m), 2.99 (3H, s), 3.04-3.09 (1H, m), 3.91 (2H, d, J = 1.4 Hz), 4.20-4.21 (2H, m), 4.58-4.63 (1H, m), 6.65 (2H, d, J = 8.1 Hz), 6.75 (1H, t, J = 7.3 Hz), 6.88-6.93 (2H, m), 6.99-7.10 (2H, m), 7.12-7.18 (2H, m), 7.67 (1H, d, J = 1.2 Hz), 7.73 (1H, dd, J = 9.2, 2.1 Hz), 8.58 (1H, t, J = 5.8 Hz). 175 CD₃OD 400 1.31 (6H, d, J = 6.5 Hz), 1.39 (3H, d, J = 6.6 Hz), 2.69 (3H, s), 2.93-3.03 (1H, m), 3.07-3.13 (1H, m), 3.52 (1H, s, br), 4.01 (1H, q, J = 6.6 Hz), 4.17-4.28 (2H, m), 4.57-4.61 (1H, m), 4.86 (3H, s), 6.97 (1H, d, J = 9.1 Hz), 7.02-7.05 (1H, m), 7.11-7.24 (2H, m), 7.74-7.79 (2H, m), 8.71-8.82 (1H, m) 176 CD₃OD 400 1.26 (6H, d, J = 6.64 Hz), 1.51 (3H, d, J = 6.85), 2.64 (3H, s), 2.90-2.98 (2H, m), 3.07-3.17 (1H, m), 3.94 (1H, q, J = 6.8 Hz), 4.16-4.21 (1H, m), 4.27-4.31 (1H, m), 4.60-4.80 (1H, m), 4.86 (3H, s), 6.97 (1H, d, J = 9.2 Hz), 7.05-7.07 (1H, m), 7.14-7.22 (2H, m), 7.74-7.84 (2H, m), 8.70-8.89 (1H, m) 178 CD₃ OD 400 0.43-0.54 (1H, m), 0.58-0.65 (6H, m), 0.97-1.10 (1H, m), 1.78-1.83 (1H, m), 2.64 (6H, s), 2.66-2.72 (1H, m), 2.89-2.99 (2H, m), 3.45-3.53 (2H, m), 3.96-4.08 (2H, m), 4.31-4.37 (1H, m), 6.76 (1H, d, J = 9.4 Hz), 6.86-6.88 (1H, m), 6.93-7.00 (2H, m), 7.55 (1H, d, J = 1.2 Hz), 7.60 (1H, dd, J = 2.1, 9.2 Hz), 8.51-8.59 (2H, m) 179 CD₃OD 400 1.07 (9H, s), 3.00 (6H, s), 3.08-3.17 (2H, m), 3.62 (1H, s), 4.21-4.29 (2H, m), 4.52-4.58 (1H, m), 4.86 (2H, s), 6.97 (1H, d, J = 9.1 Hz), 7.06-7.09 (1H, m), 7.14-7.21 (2H, m), 7.76-7.79 (2H, m), 8.74-8.77 (1H, m), 8.94-8.96 (1H, m) 180 CD₃OD 400 1.32 (6H, d, J = 8.0 Hz), 2.62-2.68 (5H, m), 2.84-2.95 (2H, m), 3.11-3.16 (2H, m), 3.81-3.86 (2H, m), 4.23 (3H, d, J = 4.0 Hz), 4.59-4.66 (2H, m), 6.95-7.04 (3H, m), 7.23-7.27 (2H, m), 7.69-7.77 (1H, m), 7.83 (1H, dd, J = 8.0, 4.0 Hz), 8.70 (1H, t, J = 8.0 Hz) 181 CD₃OD 400 1.14-1.18 (2H, m), 1.23 (6H, d, J = 6.6 Hz), 1.28-1.39 (2H, m), 1.50 (3H, d, J = 6.9 Hz), 2.61 (3H, s), 2.85-2.94 (1H, m), 3.11-3.25 (1H, m), 3.91 (1H, t, J = 6.7 Hz), 4.18 (1H, d, J = 15.1 Hz), 4.28 (1H, d, J = 15.1 Hz), 4.58-4.78 (1H, m), 4.86 (1H, s), 6.92-6.96 (1H, m), 6.98-7.04 (2H, m), 7.25-7.28 (2H, m), 7.74-7.78 (2H, m) 182 CD₃OD 400 0.67-0.76 (1H, m), 0.83-0.87 (6H, m), 1.18-1.24 (1H, m), 1.99-2.05 (1H, m), 2.87 (6H, s), 2.89-2.97 (1H, m), 3.12-3.17 (1H, m), 3.62 (1H, d, J = 5.0 Hz), 4.28 (2H, d, J = 5.7 Hz), 4.58 (1H, t, J = 4.2 Hz), 4.86 (3H, s), 6.96-7.06 (3H, m), 7.27-7.30 (2H, m), 7.75-7.80 (2H, m), 8.73-8.76 (1H, m) 183 CD₃OD 400 1.05 (9H, s), 2.90-2.98 (1H, m), 3.00 (6H, s), 3.08-3.17 (1H, m), 3.59 (1H, s), 4.23 (2H, d, J = 5.8 Hz), 4.52-4.60 (1H, m), 4.86 (3H, s), 6.89-7.03 (3H, m), 7.26-7.29 (2H, m), 7.73-7.76 (2H, m), 8.71-8.73 (1H, m) 184 CD₃OD 400 1.25-1.50 (6H, m), 2.40-2.60 (1H, m), 2.65-2.80 (1H, m), 3.00-3.20 (2H, m), 3.25-3.40 (3H, m), 4.05-4.40 (4H, m), 4.85-5.05 (2H, m), 6.70-7.00 (3H, m), 7.05-7.20 (3H, m), 7.25-7.35 (3H, m), 7.65-7.80 (2H, m), 8.60-8.70 (1H, m) 185 CD₃OD 400 2.49-2.55 (1H, m), 2.70-2.81 (1H, m), 2.99 (6H, s), 3.02-3.08 (1H, m), 3.33-3.37 (1H, m), 3.99-4.03 (1H, m), 4.18-4.24 (3H, m), 4.87 (3H, s), 6.73-6.76 (1H, m), 6.82-6.90 (1H, m), 6.95 (1H, dd, J = 1.8, 8.3 Hz), 7.03-7.10 (1H, m), 7.15-7.18 (2H, m), 7.21-7.27 (3H, m), 7.72-7.75 (2H, m), 8.55-8.68 (1H, m) 186 CD₃OD 270 0.8-2.1 (31H, m), 2.49 (3H, s), 3.6-3.9 (1H, m), 4.20-4.50 (3H, m), 6.7-6.9 (1H, m), 7.70-7.85 (1H, m), 7.9-8.1 (1H, m) 187 CD₃OD 270 0.7-1.91 (33H, m), 2.56 (3H, s), 3.70-3.90 (1H, s), 4.20-4.55 (3H, m), 6.7-6.9 (1H, m), 7.7-7.9 (1H, m), 8.5-8.9 (1H, m) 188 d6DMSO 270 0.8-1.0 (6H, m), 1.1-1.3 (1H, m), 1.5-1.8 (1H, m), 2.4-2.8 (9H, m), 2.8-2.9 (1H, m), 3.0-3.1 (1H, m) 3.2-3.7 (3H, m), 4.0-4.2 (1H, m), 4.7-4.8 (1H, m), 6.85 (1H, d, J = 7 Hz), 7.2-7.3 (1H, m), 7.5-7.6 (2H, m), 7.7-7.8 (1H, m), 8.5-8.6 (1H, m), 8.75-8.8 (1H, m). 189 CD₃OD 270 3.6-4.0 (1H, m), 4.1-4.4 (6H, m), 4.7-5.2 (5H, m), 5.9-6.3 (5H, m), 6.4-6.6 (1H, m), 8.5-8.7 (1H, m), 8.9-9.1 (1H, m), 9.2-9.3 (2H, m), 9.4-9.7 (1H, m), 10.6-10.5 (1H, m) 190 CD₃OD 270 1.7-2.3 (4H, m), 2.4-2.7 (5H, m), 2.8-3.4 (7H, m), 3.6-3.8 (1H, m), 4.0-4.4 (3H, m), 4.6-4.8 (1H, m) 6.7-6.9 (1H, m), 7.0-7.2 (1H, m), 7.3-7.4 (2H, m), 7.6-7.9 (1H, m) 8.6-8.9 (1H, m) 191 d6DMSO 270 2.4-2.6 (3H, s), 2.6-2.8 (9H, m), 4.1 (3H, s), 4.4-4.6 (1H, s), 6.8-6.9 (1H, m), 7.2-7.4 (1H, m), 7.4-7.8 (5H, m) 192 d⁶DMSO 270 2.43 (3H, s), 2.4 (3H, s), 2.5-2.9 (2H, m), 3.5-3.8 (3H, m), 4.0-4.4 (3H, m), 4.5-4.7 (2H, m), 6.8-6.9 (1H, m), 7.1-7.2 (1H, m), 7.4-7.6 (2H, m), 7.8-7.9 (1H, m), 8.8-8.9 (1H, m), 9.0-9.1 (1H, m) 193 CD₃OD 270 2.3 (3H, s), 2.6 (4H, s), 2.7-2.8 (3H, m), 2.9-3.15 (3H, m), 3.3-3.4 (3H, m), 4.0-4.4 (5H, br, m), 6.7 (1H, d, J = 7 Hz), 6.9-7.0 (1H, m), 7.1-7.2 (3H, m), 7.25-7.3 (4H, m), 7.4-7.5 (1H, m), 7.6-7.7 (1H, m) 194 CD₃OD 270 2.4-2.6 (3H, s), 2.7-3.2 (4H, m), 3.2-3.2 (5H, m), 4.0-4.1 (3H, m), 4.2-4.4 (2H, m), 4.5-4.6 (1H, m) 6.8-6.9 (1H, m), 7.0-7.3 (5H, m), 7.2-7.4 (2H, m), 7.6-7.8 (1H, m) 195 CD₃OD 270 2.3-2.4 (4H, m), 2.6-3.1 (4H, m), 3.3-3.4 (5H, m), 4.0-4.1 (2H, m), 4.2-4.3 (1H, m), 4.1-4.5 (1H, m) 6.8-6.9 (1H, m), 7.0-7.3 (3H, m), 7.3-7.6 (4H, m), 7.7-7.9 (1H, s) 196 CD₃OD 270 2.4-2.5 (4H, m), 2.8-3.1 (3H, m), 3.15-3.2 (1H, m), 3.2-3.3 (3H, m), 4.0-4.1 (1H, m), 4.2-4.4 (3H, m) 4.5-4.8 (1H, m), 6.85 (1H, d, J = 7 Hz), 7.1-7.2 (1H, m), 7.3-7.4 (2H, m), 7.45-7.5 (1H, m), 7.6-7.8 (1H, m), 8.0-8.1 (1H, m) 8.6-8 (3H, m) 197 CD₃OD 270 3.0-3.1 (4H, m), 4.1-4.4 (3H, m), 4.7-4.9 (2H, m), 5.75 (2H, s), 6.25 (2H, d, J = 7 Hz), 6.45 (2H, d, J = 7H), 7.0-7.4 (9H, m), 9.8-9.9 (1H, m) 198 CD₃OD 270 0.7-0.95 (2H, m), 1.0-1.25 (2H, m), 1.3-1.5 (3H, m), 1.6-2.0 (3H, m), 2.4-2.6 (3H, m), 2.8-3.0 (1H, m), 3.1-3.4 (8H, m) 3.5-3.8 (1H, m), 4.1-4.4 (3H, m), 4.6-4.8 (1H, m), 6.7-6.9 (1H, m), 7.1-7.3 (1H, m), 74-7.6 (2H, m), 7.7-7.8 (1H, m) 199 CD₃OD 270 2.4-2.5 (4H, m), 2.8-3.1 (3H, m), 3.15-3.2 (1H, m), 3.2-3.3 (3H, m), 4.0-4.1 (1H, m), 4.2-4.4 (3H, m) 4.5-4.8 (1H, m), 6.85 (1H, d, J = 7 Hz), 7.1-7.2 (1H, m), 7.3-7.4 (2H, m), 7.45-7.5 (1H, m), 7.6-7.8 (1H, m), 8.0-8.1 (1H, m) 8.6-8.8 (3H, m) 200 d⁶DMSO 270 1.0-1.3 (6H, m), 1.4-1.7 (5H, m), 2.4 (3H, s), 2.6 (2H, s), 2.7-2.9 (1H, m), 3.0-3.1 (1H, m), 3.7-3.8 (1H, m), 4.0-4.3 (2H, m), 4.7-4.8 (1H, m) 6.8-6.9 (1H, m), 7.1-7.2 (1H, m), 7.4-7.6 (2H m), 7.7 (1H, d, J = 8 Hz), 7.9-8.1 (4H, m), 8.6-8.7 (1H, m) 8.9-8.0 (1H, m) 201 CD₃OD 270 1.8-1.9 (2H, m), 2.0-2.1 (1H, m), 2.4-2.5 (3H, s), 2.8-3.1 (3H, m), 3.2-3.3 (8H, m), 3.7-3.8 (1H, m), 4.9-5.1 (1H, m) 6.7-6.9 (1H, m), 7.1-7.2 (1H, m), 7.3-7.4 (2H, m), 7.6-7.8 (1H, m) 202 CD₃OD 270 2.4 (3H, s), 2.7-3.0 (3H, m), 3.1-3.2 (2H, m), 3.3 (3H, s), 4.0-4.4 (5H, m), 4.6-4.8 (1H, m), 6.85 (1H, d, J = 7 Hz), 7.1-7.4 (8H, m), 7.75 (1H, d, J = 7 Hz) 203 CD₃OD 270 0.8-0.9 (6H, m), 1.3-1.4 (1H, m), 1.8-1.7 (1H, m), 2.25 (3H, s), 2.6 (3H, s), 3.3-3.5 (3H, m), 3.6-3.7 (2H, m), 4.0-4.3 (2H, m), 4.8-4.9 (2H, m), 6.6 (1H, d, J = 7 Hz), 7.3-7.4 (5H, m), 7.5-7.6 (3H, m), 7.7-8.0 (2H, m), 8.2-8.3 (1H, m) 204 CD₃OD 400 1.72-1.77 (1H, m), 1.87-1.96 (1H, m), 2.10-2.17 (1H, m), 2.45 (3H, s), 2.89 (3H, s), 2.91-2.95 (1H, m), 3.07-3.10 (1H, m), 3.12-3.21 (1H, m), 3.63-3.69 (1H, m), 4.05 (1H, t, J = 8.5 Hz), 4.13-4.18 (1H, m), 4.25-4.31 (1H, m), 4.64 (1H, t, J = 8.4 Hz), 4.86 (3H, s), 6.78 (1H, d, J = 9.0 Hz), 6.96-7.00 (2H, m), 7.19-7.28 (2H, m), 7.68 (2H, d, J = 9.1 Hz), 8.65-8.67 (1H, m) 205 CD₃OD 400 1.75-1.82 (1H, m), 1.89-1.96 (1H, m), 2.14-2.18 (1H, m), 2.47 (3H, s), 2.89 (3H, s), 2.92-2.93 (1H, s), 3.06-3.11 (1H, m), 3.15-3.22 (1H, m), 3.64-3.70 (1H, m), 4.06 (1H, t, J = 8.6 Hz), 4.13-4.18 (1H, m), 4.27-4.32 (1H, m), 4.64 (1H, t, J = 8.1 Hz), 4.86 (3H, s), 6.79 (1H, d, J = 9.1 Hz), 7.00-7.07 (1H, m), 7.09-7.19 (2H, m), 7.71 (2H, d, J = 9.1 Hz), 8.67-8.69 (1H, m) 206 CD₃OD 400 1.71-1.80 (1H, m), 1.86-1.98 (1H, m), 2.10-2.20 (1H, m), 2.34 (3H, s), 2.42-2.48 (1H, m), 2.51 (3H, s), 2.88 (3H, s), 2.91-2.95 (1H, m), 3.05-3.10 (1H, m), 3.14-3.21 (1H, m), 3.64-3.70 (1H, m), 4.09 (1H, t, J = 8.4 Hz), 4.21-4.33 (2H, m), 4.60-4.65 (1H, m), 6.66 (1H, s), 7.00-7.03 (1H, m), 7.09-7.17 (2H, m), 8.47 (1H, t, J = 4.9 Hz), 8.87 (1H, d, J = 7.6 Hz) 207 CD₃OD 400 0.80 (3H, d, J = 6.8 Hz), 0.83-0.89 (4H, m), 1.27-1.36 (1H, m), 1.76-1.82 (1H, m), 2.36 (3H, s), 2.52 (3H, s), 2.60 (3H, s), 2.88-2.94 (1H, m), 3.08-3.13 (1H, m), 3.66 (1H, d, J = 4.9 Hz), 4.30 (2H, d, J = 4.8 Hz), 4.56-4.62 (1H, m), 6.67 (1H, s), 7.05-7.08 (1H, m), 7.12-7.19 (2H, m), 8.49 (1H, t, J = 4.9 Hz), 8.79 (1H, d, J = 7.5 Hz) 209 CD₃OD 270 0.70-0.94 (7H, m), 1.16-1.32 (1H, m), 1.65-1.74 (1H, m,) 2.20 (3H, s), 3.30-3.40 (1H, m), 3.62-3.72 (2H, m), 4.05-4.28 (2H, m), 4.78-4.84 (1H, m), 7.31-7.38 (2H, m), 7.45-7.57 (4H, m), 7.74-7.78 (1H, m), 7.84-7.87 (1H, m), 8.16 (1H, d, J = 8.2 Hz), 8.62 (1H, m) 210 CD₃OD 270 1.70-1.90 (3H, m), 2.05-2.30 (1H, m), 2.80-3.05 (4H, m), 3.10-3.80 (5H, m), 4.10-4.40 (2H, m), 4.45-4.60 (1H, m), 6.90-7.05 (1H, m), 7.10-7.25 (1H, m), 7.30-7.50 (2H, m), 7.65-7.85 (2H, m), 8.25-8.40 (2H, m) 211 CD₃OD 270 0.50-0.70 (3H, m), 0.75-0.90 (3H, m), 0.95-1.15 (1H, m), 1.40-1.70 (2H, m), 1.95-2.10 (1H, m), 2.80-2.95 (4H, m), 3.15-3.40 (4H, m), 3.50-3.70 (1H, m), 4.10-4.40 (2H, m), 4.50-4.70 (1H, m), 6.90-7.05 (1H, m), 7.15-7.30 (1H, m), 7.35-7.50 (1H, m), 7.65-7.90 (2H, m), 8.30-8.40 (1H, m), 8.50-8.70 (1H, m) 212 CD₃OD 270 1.25-1.40 (3H, m), 2.80-3.15 (8H, m), 3.25-3.35 (2H, m), 4.10-4.60 (4H, m), 6.90-7.00 (1H, m), 7.10-7.20 (1H, m), 7.30-7.50 (2H, m), 7.60-7.80 (2H, m), 8.15-8.30 (1H, m), 8.40-8.55 (1H, m) 213 CD₃OD 270 0.58 (2H, d, J = 6.7 Hz), 0.89 (2H, t, J = 7.2 Hz), 1.04-1.09 (1H, m), 1.53-1.56 (1H, m), 1.77-1.83 (1H, m), 2.86 (3H, s), 3.16-3.41 (3H, m), 3.86-3.90 (1H, m), 4.11-4.21 (2H, m), 4.90 (7H, s), 6.87 (1H, d, J = 9.2 Hz), 7.32-7.41 (3H, m), 7.63 (2H, d, J = 9.9 Hz), 7.86 (2H, t, J = 5.5 Hz), 8.39 (1H, t, J = 5.7 Hz), 8.71 (1H, d, J = 7.2 Hz) 214 CD₃OD 270 0.87-1.27 (18H, m), 1.30-1.80 (14H, m), 3.78-3.80 (1H, m), 4.17-4.23 (2H, m), 4.58 (1H, d, J = 9.1 Hz), 4.91 (4H, s), 6.98 (1H, d, J = 8.9 Hz), 7.81 (1H, s), 7.91 (1H, d, J = 9.2 Hz), 8.70-8.90 (1H, m) 215 CD₃OD 270 0.95-1.23 (10H, m), 1.53-1.76 (16H, m), 2.02-2.07 (4H, m), 2.40-2.60 (1H, m), 3.32-3.41 (2H, m), 4.22-4.26 (2H, m), 4.40-4.42 (1H, m), 4.61 (1H, d, J = 7.0 Hz), 6.97 (1H, d, J = 9.1 Hz), 7.76 (1H, d, J = 1.5 Hz), 7.90 (1H, dd, J = 2.9 Hz, 9.2 Hz), 8.70-8.90 (1H, m) 217 CD₃OD 270 1.11-1.22 (17H, m), 1.56-1.70 (14H, m), 3.81 (1H, s), 4.24-4.29 (2H, m), 4.59 (1H, d, J = 7.2 Hz), 4.86-4.89 (5H, m), 6.99 (1H, d, J = 9.2 Hz), 7.82 (1H, d), 7.93 (1H, dd, J = 2.0 Hz, 9.2 Hz), 8.60-8.70 (1H, m) 218 CD₃OD 270 0.98-1.28 (8H, m), 1.52 (3H, d, J = 6.9 Hz), 1.63-1.81 (14H, m), 2.65 (3H, s), 3.93-3.95 (1H, m), 4.17-4.20 (1H, m), 4.28-4.30 (1H, m), 4.60 (1H, d, J = 7.6 Hz), 4.96 (5H, s), 6.98 (1H, d, J = 9.1 Hz), 7.78 (1H, d), 7.919 (1H, dd, J = 1.9 Hz, 9.1 Hz), 8.70-8.80 (1H, m) 219 CD₃OD 270 0.97-1.28 (18H, m), 1.54-1.70 (14H, m), 2.59 (3H, s), 3.3 (1H, d, J = 4.7 Hz), 4.23-4.29 (2H, m), 4.58 (1H, d, J = 7.7 Hz), 4.90 (4H, s), 6.98 (1H, d, J = 9.1 Hz), 7.82 (1H, d, J = 1.5 Hz), 7.91 (1H, dd, J = 2.3 Hz, 9.2 Hz), 8.70-8.90 (1H, m) 220 CD₃OD 270 0.95-1.23 (8H, m), 1.52-1.73 (14H, m), 3.29-3.32 (2H, m), 3.67-3.86 (2H, m), 4.21-4.26 (1H, m), 4.63 (1H, d, J = 6.4 Hz), 4.49 (5H, s), 6.98 (1H, d, J = 9.4 Hz), 7.76 (1H, d), 7.89 (1H, dd, J = 2 Hz, 9.2 Hz), 8.60-8.70 (1H, m) 221 CD₃OD 270 1.10-1.28 (8H, m), 1.52-1.73 (14H, m), 2.72 (3H, s), 3.29-3.32 (2H, m), 3.86 (2H, dd, J = 8.9, 15.8 Hz), 4.20-4.27 (2H, m), 4.63 (1H, d, J = 6.5 Hz), 4.94 (3H, s), 6.97 (1H, d, J = 9.2 Hz), 7.76 (1H, d), 7.89 (1H, dd, J = 2.2 Hz, 7.3 Hz), 8.60-8.70 (1H, m) 222 CD₃OD 270 1.10-1.28 (8H, m), 1.52-1.73 (14H, m), 2.93 (6H, s), 3.29-3.32 (2H, m), 4.01 (2H, d), 4.20-4.27 (2H, m), 4.66 (1H, d), 4.94 (2H, s), 7.01 (1H, d, J = 9.2 Hz), 7.77 (1H, s), 7.88 (1H, d), 8.60-8.70 (1H, m) 223 400 1.09-1.30 (12H, m), 1.64-1.76 (14H, m), 2.00-2.10 (2H, m), 2.19-2.26 (1H, m), 2.57-2.63 (1H, m), 2.93 (3H, s), 3.20-3.27 (1H, m), 3.71-3.77 (1H, m), 4.17-4.24 (2H, m), 4.29-4.39 (1H, m), 4.64 (1H, d, J = 7.2 Hz), 6.99 (1H, d, J = 9.1 Hz), 7.80 (1H, d, J = 1.5 Hz), 7.92 (1H, dd, J = 2.1, 9.2 Hz), 8.74-8.77 (1H, m) 224 CD₃OD 270 0.87-0.96 (6H, m), 1.30-1.60 (1H, m), 1.70-2.10 (1H, m), 3.22-3.26 (2H, m), 3.71-3.76 (2H, m), 3.86-4.06 (1H, m), 4.51-4.53 (1H, m), 4.86 (6H, s), 6.71-6.80 (1H, m), 7.18-7.45 (7H, m), 8.35-8.55 (1H, m) 225 CD₃OD 270 0.8-0.9 (1H, m), 1.5-1.8 (1H, m), 1.9-2.1 (1H, m), 2.2-2.4 (1H, m), 2.9 (3H, s), 2.5 (3H, s), 3.0-3.1 (3H, m), 3.3 (2H, s), 3.4-3.5 (2H, m), 3.6-3.8 (1H, m), 4.2-4.4 (3H, m), 5.65 (1H, dd, J = 7 Hz), 7.0-7.1 (1H, d, J = 9 Hz), 7.15-7.3 (4H, m), 7.7-7.9 (1H, m), 8.7-8.8 (1H, m) 227 CD₃OD 270 1.19-1.78 (22H, m), 4.24-4.27 (2H, m), 4.50-4.60 (1H, m), 6.19 (1H, s), 6.89-6.97 (3H, m), 7.73 (1H, s), 6.86 (1H, dd, J = 2 Hz, 9 Hz), 7.85-7.88 (1H, m), 11.0 (1H, s, br) 228 CD₃OD 270 3.47-3.54 (1H, m), 3.64-3.72 (1H, m), 4.04-4.11 (2H, m), 4.79-4.85 (1H, m), 4.89-4.91 (3H, m), 6.16-6.19 (1H, m), 6.81-6.93 (3H, m), 7.30-7.37 (2H, m), 7.46-7.56 (4H, m), 7.72-7.76 (1H, m), 7.84-7.88 (1H, m), 8.20 (1H, d, J = 7.9 Hz), 8.40-8.60 (1H, m), 10.8-11.10 (1H, s, br) 229 CD₃OD 270 3.05-3.40 (3H, m), 4.15-4.30 (1H, m), 4.60-4.80 (1H, m), 4.90-5.00 (3H, m), 6.10-6.30 (1H, m), 6.80-7.00 (3H, m), 7.40-7.80 (3H, m), 8.55-8.70 (1H, m) 231 CD₃OD 270 2.18 (3H, s), 2.20 (3H, s), 3.54-3.60 (1H, m), 3.64-3.72 (1H, m), 4.03-4.13 (2H, m), 4.80-4.86 (1H, m), 4.89-4.91 (2H, m), 5.71 (1H, d, J = 2.5 Hz), 6.16-6.19 (1H, m), 6.83 (1H, d, J = 8.9 Hz), 7.33-7.367 (2H, m), 7.476-7.54 (4H, m), 7.75-7.78 (1H, m), 7.85-7.886 (1H, m), 8.21 (1H, d, J = 7.7 Hz), 8.40-8.60 (1H, m), 10.8-11.10 (1H, s, br) 232 CD₃OD 270 2.17 (3H, s), 2.19 (3H, s), 3.10-3.40 (4H, m), 4.15-4.30 (1H, m), 4.60-4.80 (1H, m), 4.90-5.10 (1H, m0, 5.71 (1H, s), 6.93 (1H, d, J = 9.15 Hz), 7.40-7.80 (6H, m), 8.60-8.80 (1H, m), 10.30-10.50 (1H, m) 233 CD₃OD 270 2.10-2.30 (6H, m), 3.00-3.20 (2H, m), 3.25-3.40 (2H, m), 4.05-4.30 (2H, m), 4.70-4.85 (1H, m), 4.90-5.10 (1H, m), 5.72 (1H, s), 6.90-7.00 (1H, m), 7.10-7.25 (1H, m), 7.30-7.50 (2H, m), 7.65-7.80 (2H, m), 8.60-8.70 (1H, m0, 10.40-10.55 (1H, m) 234 CD₃OD 270 2.18 (3H, s), 2.19 (3H, s), 2.27 (3H, s), 2.90-3.10 (2H, m), 3.25-3.35 (2H, m), 3.50-3.70 (1H, m), 4.15-4.30 (2H, m), 4.60-4.75 (1H, m), 5.71 (1H, s), 6.85-7.30 (5H, m), 7.60-7.80 (2H, m), 8.50-8.70 (1H, m), 10.30-40.50 (1H, m) 235 CD₃OD 270 2.20 (6H, s), 3.00-3.35 (4H, m), 4.10-4.30 (2H, m), 4.60-4.75 (1H, m), 4.90-5.10 (1H, m), 5.72 (1H, s), 6.94 (1H, d, J = 9.15 Hz), 7.10-7.30 (4H, m), 7.60-7.80 (2H, m), 8.60-8.75 (1H, m), 10.30-10.50 (1H, m) 236 CD₃OD 270 2.19 (6H, m), 3.00-3.40 (3H, m), 4.10-4.40 (2H, m), 4.60-4.80 (1H, m), 4.90-5.10 (2H, m), 5.72 (1H, s), 6.85-7.40 (5H, m), 7.60-7.80 (2H, m), 8.55-8.70 (1H, m), 10.40-10.50 (1H, m) 237 CD₃OD 270 2.19 (6H, s), 3.07-3.20 (2H, m), 3.25-3.40 (3H, m), 4.05-4.40 (2H, m), 4.60-4.80 (1H, m), 5.71 (1H, s), 6.91-6.94 (1H, m), 7.23 (4H, s), 7.65-7.71 (3H, m), 8.50-8.70 (1H, m), 10.40-10.60 (1H, m) 238 d6- 270 1.3-1.8 (7H, m), 2.1-2.3 (6H, m), 2.5-2.6 (4H, DMSO m), 3.1-3.4 (3H, m), 4.2-4.3 (1H, d, J = 7 Hz), 6.7 (1H, s), 6.9-7.0 (1H, m), 7.2-7.3 (1H, m), 7.7-8.1 (3H, m), 8.6-8.7 (1H, m), 10.9-11 (1H, s) 239 CD₃OD 270 2.19 (3H, s), 2.20 (3H, s), 3.20-3.30 (2H, m), 4.20-4.21 (2H, m), 4.78 (1H, t, J = J = 7.7 Hz), 5.71 (1H, s), 6.93 (1H, d, J = 9.1 Hz), 7.18-7.38 (7H, m), 7.68 (1H, s), 7.73-7.77 (1H, m), 8.50-8.70 (1H, m), 10.35-10.55 (1H, m) 240 CD₃OD 270 2.19 (6H, s), 3.25-3.36 (2H, m), 4.21-4.23 (2H, m), 4.75 (1H, t, J = J = 7.4 Hz), 4.89 (2H, s), 5.71 (1H, s), 6.93 (1H, d, J = 9.2 Hz), 7.40-7.51 (3H, m), 7.66-7.78 (4H, m), 8.50-8.70 (1H, m), 10.35-10.55 (1H, m) 241 CD₃OD 270 2.14 (3H, s), 2.18 (3H, s), 3.20-3.40 (4H, m), 4.00-4.30 (2H, m), 4.65-4.90 (1H, m), 4.95-5.05 (2H, m), 5.70 (1H, s), 6.70-7.60 (8H, m), 8.35-8.50 (1H, m), 10.30-10.50 (1H, m) 242 CD₃OD 270 2.10-2.30 (6H, m), 2.80-3.50 (5H, m), 4.20-4.40 (2H, m), 4.50-4.70 (1H, m), 5.71 (1H, s), 6.80-7.10 (3H, m), 7.10-7.30 (2H, m), 7.60-7.80 (2H, m), 8.50-8.70 (1H, m), 10.30-10.50 (1H, m) 243 CD₃OD 270 2.00-2.10 (1H, m), 2.15-2.30 (6H, m), 2.95-3.20 (2H, m), 3.25-3.35 (2H, m), 4.10-4.30 (2H, m), 4.60-4.70 (1H, m), 5.71 (1H, s), 6.90-7.20 (4H, m), 7.70-7.80 (2H, m), 8.60-7.70 (1H, m), 10.40-40.50 (1H, m) 244 CD₃OD 270 2.21 (6H, s), 2.35 (3H, s), 3.12-3.15 (2H, m), 4.14-4.20 (2H, m), 4.60-4.75 (1H, m), 4.89 (3H, s), 5.72 (1H, s), 6.90 (1H, d, J = 9.2 Hz), 7.11-7.13 (5H, m), 7.61-7.65 (2H, m), 8.50-8.70 (1H, m) 245 CD₃OD 270 2.20 (3H, s), 2.22 (3H, s), 3.08-3.15 (2H, m), 4.22 (1H, s), 4.68-4.735 (1H, m), 4.89 (3H, s), 5.72 (1H, s), 6.95 (1H, d, J = 8.4 Hz), 7.11-7.20 (3H, m), 7.74-7.81 (2H, m), 8.60-8.80 (1H, m), 10.43 (1H, s, br) 246 CD₃OD 270 2.19 (6H, s) 3.03-3.10 (2H, m) 4.09-4.26 (2H, m) 4.67 (1H, t, J = 7.4 Hz) 4.92 (5H, s) 5.71 (1H, s) 6.92 (1H, d, J = 9.9 Hz) 7.16-7.24 (4H, m) 7.67 (2H, d, J = 7.4 Hz) 247 CD₃OD 270 2.19 (6H, s) 3.00 (2H, br s) 3.31 (1H, s) 4.11-4.27 (2H, m) 4.60 (1H, t, J = 7.2 Hz) 4.91 (5H, s) 5.71 (1H, s) 6.07 (2H, d, J = 7.9 Hz) 6.92 (1H, d, J = 9.4 Hz) 7.02 (2H, d, J = 7.6 Hz) 8.55 (1H, s) 10.45 (1H, s) 248 CD₃OD 270 2.19 (3H, s) 2.21 (3H, s) 3.08-3.13 (2H, m) 3.30 (1H, s) 4.22-4.24 (2H, m) 4.69 (1H, t, J = 7.2 Hz) 4.90 (2H, s) 5.72 (1H, s) 6.95 (1H, d, J = 9.2 Hz) 7.05-7.17 (2H, m) 7.73-7.81 (2H, m) 8.69 (1H, t, J = 5.6 Hz) 10.43 (1H, s) 249 CD₃OD 270 2.20 (6H, s) 3.08-3.12 (2H, m) 3.30 (1H, s) 4.18-4.25 (2H, m) 4.69 (1H, t, J = 7.2 Hz) 4.90 (2H, s) 5.72 (1H, s) 6.79-6.83 (4H, m) 7.72-7.78 (2H, m) 8.67 (1H, s) 10.44 (1H, s) 250 CD₃OD 270 2.19 (6H, s) 3.31-3.42 (2H, m) 4.03-4.18 (2H, m) 4.90 (3H, s) 5.71 (1H, s) 6.81 (1H, d, J = 8.4 Hz) 7.34 (2H, s) 7.57 (2H, s) 7.86 (2H, s) 8.57 (1H, s) 10.46 (1H, s) 251 d6- 270 2.2 (6H, s), 2.5 (3H, s), 3.0-3.3 (1H, m), DMSO 4.0-4.2 (1H, m), 4.7-4.8 (1H, m), 5.7 (1H, s), 6.9-7.0 (1H, d, j = 7 Hz), 7.3 (1H, d, j = 7 Hz), 7.7-7.8 (2H, m), 8.0-8.1 (1H, m), 8.6-8.8 (1H, m), 10.9-11.0 (1H, m). 252 d6- 270 2.1-2.3 (7, m), 2.5-2.6 (3H, m), 2.8-3.1 (2H, m), DMSO 4.0-4.2 (2H, m), 4.5-4.6 (1H, m), 5.7 (1H, s), 6.9-7.0 (1H, m) 7.0-7.2 (4H, m), 7.3-7.4 (1H, m), 7.6-7.8 (2H, m), 8.0-8.1 (1H, m), 8.6-8.7 (1H, m), 10.9-11 (1H, m) 253 d6- 270 1.2 (9H, s), 2.1-2.15 (4H, d, j = 7 Hz), 2.5 (6H, s), DMSO 2.8-3.1 (2H, m), 4.1-4.2 (2H, m), 4.6 (1H, m), 5.6 (1H, s), 6.9-7.0 (1H, d, j = 9 Hz), 7.1-7.4 (4H, m), 7.8-7.9 (1H, m), 8.0 (1H, s), 8.6 (1H, m) 254 d6- 270 2.1 (6H, s), 2.5 (3H, s), 2.8-3.1 (3H, m), DMSO 4.1-4.2 (2H, m), 4.6-4.8 (1H, m), 5.7 (1H, s), 6.7-6.8 (2H, m), 6.9-7.0 (1H, d, j = 7 Hz), 7.1-7.2 (2H, m), 7.25-7.30 (1H, d, j = 7 Hz). 7.7-7.9 (2H, m), 8.0-8.1 (1H, m), 8.6-8.7 (1H, m), 10.9 (1H, s) 255 d6- 270 1.4-1.5 (3H, t, j = 7 Hz), 2.2 (6H, s), 2.9-3.1 (1H, DMSO m), 3.3 (5H, s), 3.9-4.1 (2H, q, j = 7 Hz), 4.1-4.3 (1H, m), 4.6-4.8 (1H, m), 5.8 (1H, s), 6.8-6.9 (2H, d, j = 9 Hz), 6.91-6.94 (1H, d, j = 9 Hz), 7.0-7.11 (2H, d, j = 9 Hz), 7.7-7.8 (2H, m) 8.5-8.6 (1H, m), 10.5 (1H, s) 256 CD₃OD 270 1.2 (9H, s), 2.1-2.15 (4H, d, j = 7 Hz), 2.5 (6H, s), 2.8-3.1 (2H, m), 4.1-4.2 (2H, m), 4.6 (1H, m), 5.6 (1H, s), 6.9-7.0 (1H, d, j = 9 Hz), 7.1-7.4 (4H, m), 7.8-7.9 (1H, m), 8.0 (1H, s), 8.6 (1H, m) 257 CD₃OD 400 2.07 (3H, s) 2.09 (3H, s) 3.22-3.24 (1H, m) 3.52-3.64 (1H, m) 3.69-3.75 (1H, m) 4.13-4.37 (2H, m) 4.81 (3H, br s) 5.02-5.05 (1H, M) 5.61 (1H, m) 6.76 (1H, d, J = 8.0 Hz) 7.40 (1H, s) 7.52-7.75 (4H, m) 7.80-7.90 (1H, m) 7.92-8.02 (2H, m) 8.66 (1H, t, J = 8.0 Hz) 258 CD₃OD 400 2.24 (3H, s) 3.20-3.25 (1H, m) 3.30-3.36 (1H, m) 4.23-4.33 (2H, m) 4.81 (1H, t, J = 8.0 Hz) 4.92 (4H, br s) 6.05-6.06 (1H, m) 6.85 (1H, d, J = 4.0 Hz) 6.99 (1H, d, J = 8.0 Hz) 7.47 (2H, d, J = 8.0 Hz) 7.60 (2H, d, J = 8.0 Hz) 7.79-7.82 (2H, m) 10.86 (1H, s) 259 CD₃OD 270 2.06 (3H, s) 3.04-3.13 (3H, m) 4.16-4.18 (2H, m) 4.66 (1H, t, J = 7.7 Hz) 4.93 (2H, s) 6.66 (2H, d, J = 6.9 Hz) 6.89 (1H, d, J = 9.9 Hz) 7.14-7.24 (4H, m) 10.6 (1H, s) 260 CD₃OD 270 2.06 (3H, s) 3.01-3.18 (3H, m) 4.17 (2H, s) 4.63 (1H, t, J = 7.8 Hz) 4.91 (3H, br s) 6.65 (2H, d, J = 7.4 Hz) 6.88-6.98 (3H, m) 7.20-7.25 (2H, m) 7.68 (2H, d, J = 6.4 Hz) 10.6 (1H s) 261 CD₃OD 400 2.25 (3H, s) 3.16-3.30 (3H, m) 4.17-4.26 (2H, m) 4.68 (1H, t, J = 8.0 Hz) 4.94-4.99 (4H, m) 6.00-6.01 (1H, m) 6.99-7.01 (3H, m) 7.21-7.25 (2H, m) 7.72-7.75 (2H, m) 10.72 (1H, s) 262 CD₃OD 400 2.30 (3H, s) 3.26-3.46 (2H, m) 4.30 (2H, d, J = 4.0 Hz) 4.86 (1H, t, J = 8.0 Hz) 4.91 (4H, br s) 6.05 (1H, d, J = 4.0 Hz) 6.83 (1H, s) 6.95 (1H, d, J = 8.0 Hz) 7.20-7.27 (2H, m) 7.32-7.46 (2H, m0 7.72-7.77 (2H, m) 10.75 (1H, s) 263 CD₃OD 400 2.29 (3H, s) 3.12-3.37 (2H, m) 4.22 (2H, d, J = 4.0 Hz) 4.84 (1H, t, J = 8.0 Hz) 4.99-5.08 (5H, m 0 6.05 (1H, d, J = 4.0 Hz) 6.78-6.85 (1H, m) 6.98-7.07 (1H, m) 7.22-7.24 (1H, m) 7.43 (1H, t, J = 4.0 Hz) 7.75-7.80 (2H, m) 10.76 (1H, s) 264 CD₃OD 400 2.32 (3H, s) 3.12-3.19 (2H, m) 4.19-4.35 (2H, m) 4.76 (1H, t, J = 4.0 Hz) 4.93 (4H, br s) 6.06 (1H, s) 6.858 (1H, t, J = 4.0 Hz) 7.00 (1H, dd, J = 8.0, 4.0 Hz) 7.20-7.29 (1H, m) 7.41-7.48 (2H, m) 7.74-7.78 (2H, m) 10.75 (1H, br s) 265 CD₃OD 400 2.30 (3H, s) 3.12-3.31 (2H, m) 4.19-4.39 (2H, m) 4.82 (1H, t, J = 4.0 Hz) 5.00 (4H, br s) 6.04 (1H, d, J = 4.0 Hz) 6.83 (1H, s) 6.98-7.04 (3H, m) 7.08-7.10 (1H, m) 7.25-7.32 (1H, m) 7.72-7.85 (2H, m) 10.80 (1H, s) 266 CD₃OD 400 2.27 (3H, s) 3.12-3.30 (2H, m) 4.20-4.37 (2H, m) 4.77 (1H, t, J = 8.0 Hz) 5.01 (4H, s) 6.05 (1H, t, J = 4.0 Hz) 6.84 (1H, t, J = 4.0 Hz) 6.97 (1H, d, J = 8.0 Hz) 7.21-7.24 (1H, m) 7.27-7.33 (3H, m) 7.74-7.77 (2H, m) 10.79 (1H, s) 267 CD₃OD 400 2.28 (3H, s) 3.07-3.20 (2H, m) 4.19-4.35 (2H, m) 4.75 (1H, t, J = 8.0 Hz) 5.07 (4H, s) 6.06 (1H, d, J = 4.0 Hz) 6.85 (1H, d, J = 4.0 Hz) 7.00 (1H, d, J = 8.0 Hz) 7.22-7.38 (4H, m) 7.73-7.79 (2H, m) 10.77 (1H, s) 268 CD₃OD 400 2.27 (3H, s) 2.30 (3H, s) 3.10-3.29 (2H, m) 4.19-4.27 (2H, m) 4.77 (1H, t, J = 8.0 Hz) 5.24 (4H, s) 6.04 (1H, s) 6.82 (1H, s) 6.92-6.95 (1H, m) 7.04-7.09 (3H, m) 7.15-7.27 (1H, m) 7.68-7.74 (2H, m) 10.80 (1H, s) 269 CD₃OD 400 2.23 (3H, s) 3.12-3.26 (2H, m) 4.22-4.46 (2H, m) 4.78 (1H, t, J = 4.0 Hz) 4.93 (4H, s) 6.05 (1H, t, J = 4.0 Hz) 6.84 (1H, t, J = 4.0 Hz) 6.91-7.04 (3H, m) 7.11-7.17 (1H, m) 7.26-7.34 (1H, m) 7.75-7.80 (2H, m) 10.86 (1H, s) 270 CD₃OD 400 2.31 (3H, s) 3.05-3.15 (2H, m) 4.26-4.39 (2H, m) 4.60 (1H, t, J = 8.0 Hz) 4.93 (4H, br s) 6.06 (1H, s) 6.82-6.89 (4H, m) 7.00 (1H, d, J = 8.0 Hz) 7.78 (1H, s) 7.83 (1H, dd, J = 8.0, 4.0 Hz) 10.76 (1H, s) 271 CD₃OD 400 2.27 (3H, s) 3.15-3.25 (1H, m) 3.33-3.37 (1H, m) 4.32 (2H, s) 4.81 (1H, t, J = 8.0 Hz) 4.95 (4H, br s) 6.04 (1H, s) 6.83 (1H, s) 7.08 (1H, d, J = 8.0 Hz) 7.48-7.61 (4H, m) 7.71-7.88 (2H, m) 10.86 (1H, s) 272 CD₃OD 400 2.24 (3H, s) 3.20-3.25 (1H, m) 3.30-3.36 (1H, m) 4.23-4.33 (2H, m) 4.81 (1H, t, J = 8.0 Hz) 4.92 (4H, br s) 6.05-6.06 (1H, m) 6.85 (1H, d, J = 4.0 Hz) 6.99 (1H, d, J = 8.0 Hz) 7.47 (2H, d, J = 8.0 Hz) 7.60 (2H, d, J = 8.0 Hz) 7.79-7.82 (2H, m) 10.86 (1H, s) 273 CD₃OD 400 0.96-1.08 (2H, m), 1.20-1.30 (3H, m), 1.43-1.51 (1H, m), 1.71-1.89 (7H, m), 2.40 (3H, s), 4.29-4.39 (2H, m), 4.55-4.61 (1H, m), 4.95 (4H, s), 6.08 (1, d, J = 2.3 Hz), 6.86 (1H, t, J = 2.7 Hz), 7.03 (1H, d, J = 9.5 Hz) 7.82 (1H, d, J = 1.04 Hz) 7.9 (1H, dd, J = 9.24, 2.12 Hz) 8.70-8.81 (1H, m) 274 CD₃OD 270 3.26-3.30 (1H, m) 3.82 (3H, s) 4.17 (2H, s) 4.75-4.89 (7H, m) 6.53 (1H, d, J = 8.4 Hz) 6.79 (2H, s) 7.31 (1H, dd, J = 6.5, 2.2 Hz) 7.41-7.48 (3H, m) 7.60 (1H, s) 7.75 (1H, d, J = 1.7 Hz) 275 CD₃OD 270 3.25-3.32 (2H, m) 4.11-4.23 (1H, m) 4.68-4.75 (1H, m) 4.90 (7H, br s) 6.83-6.84 (2H, m) 6.92 (1H, d, J = 9.2 Hz) 7.48-7.57 (3H, m) 7.71-7.74 (2H, m) 8.68 (1H, d, J = 5.3 Hz) 276 CD₃OD 270 2.21 (3H, s) 3.18-3.30 (3H, m) 4.21 (2H, s) 4.74 (1H, t, J = 7.4 Hz) 4.93 (5H, br s) 6.63 (1H, s) 6.91 (1H, d, J = 9.1 Hz) 7.48-7.56 (3H, m) 7.69-7.71 (2H, m) 8.73 (1Hs) 277 CD₃OD 270 1.8-1.9 (2H, m), 2.2-2.4 (6H, m), 3.2-3.3 (2H, m), 4.1-4.4 (4H, m), 4.7-4.9 (1H, m), 5.7-5.8 (1H, m) 6.2-6.4 (2H, m), 6.7-6.8 (1H, m), 7.1-7.2 (1H, m) 7.3-7.4 (4H, m), 7.5-7.6 (2H, m) 278 CD₃OD 270 2.1 (4H, s), 2.2 (1H, s), 2.5 (5H, s), 4.0-4.1 (1H, m), 4.7-4.9 (1H, m), 5.6 (1H, s), 6.5-6.7 (1H, m), 7.4-7.6 (8H, m), 7.9-8.1 (2H, m), 8.3-8.4 (1H, m), 8.6-8.7 (1H, m), 9.9-10 (1H, m), 11 (1H, s) 279 CD₃OD 270 1.3-1.5 (6, m), 3.0 (5H, m), 4.1-4.4 (2H, m), 4.7-4.9 (2H, m), 5.8 (1H, s), 6.2 (1H, d, J = 7 Hz), 6.5 (1H, d, J = 7 Hz), 7.0-7.4 (7H, m), 9.8 (1H, m) 280 CD₃OD 270 1.3-1.5 (6, m), 3.0 (5H, m), 4.1-4.4 (2H, m), 4.7-4.9 (2H, m), 5.8 (1H, s), 6.2 (1H, d, J = 7 Hz), 6.5 (1H, d, J = 7 Hz), 7.0-7.4 (7H, m), 9.8 (1H, m) 281 CD₃OD 270 2.2 (6H, s), 2.3 (2H, s), 2.4 (3H, s), 3.0-3.1 (2H, m), 3.3 (3H, s), 4.0-4.4 (2H, m), 4.7-4.8 (1H, m), 5.7 (1H, s), 6.7 (1H, d, J = 7 Hz), 7.0-7.3 (5H, m), 7.6 (1H, d, J = 7 Hz), 8.5 (1H, m), 10.5-10.8 (1H, m) 282 CD₃OD 270 2.17 (6H, d, J = 3.2 Hz) 2.37 (3H, s) 3.24-3.33 (2H, m) 4.14-4.18 (2H, m) 4.78 (1H, t, J = 7.7 Hz) 4.98 (1H, s) 5.69 (1H, s) 6.71 (1H, d, J = 9.2 Hz) 7.44-7.48 (4H, m) 7.65-7.68 (3H, m) 8.57 (1H, t, J = 5.4 Hz) 10.46 (1H, s) 286 CD₃OD 400 2.36 (3H, s) 2.49 (3H, s) 3.10-3.23 (2H, m) 4.17-4.22 (1H, m) 4.29-4.38 (1H, m) 4.76 (1H, t, J = 8.0 Hz) 4.93 (3H, br s) 6.05 (1H, s) 6.79-6.84 (2H, m) 7.05-7.07 (1H, m) 7.11-7.20 (2H, m) 7.74 (1H, d, J = 8.0 Hz) 8.67 (1H, t, J = 4.0 Hz) 10.89 (1H, br s) 287 CD₃OD 270 3.10-3.15 (1H, m) 3.29-3.32 (1H, m) 4.19 (1H, q, J = 6.7 Hz) 4.72 (1H, t, J = 7.7 Hz) 4.91 (5H, br s) 6.92-6.99 (3H, m) 7.21-7.26 (2H, m) 7.40-7.41 (2H, m) 7.68 (2H, br s) 7.71 (1H, d, J = 2.2 Hz) 288 CD₃OD 270 3.11-3.19 (1H, m) 3.30 (1H, s) 4.20 (1H, q, J = 8.9 Hz) 4.76 (1H, t, J = 7.4 Hz) 4.95 (6H, br s) 6.91-6.98 (3H, m) 7.05 (1H, d, J = 7.7 Hz) 7.22-7.27 (1H, m) 7.47 (2H, s) 7.68-7.73 (2H, m) 289 CD₃OD 270 3.30 (1H, br s) 3.57-3.68 (1H, m) 3.97-4.18 (1H, m) 4.91 (7H, br s) 6.82 (1H, d, J = 9.2 Hz) 7.32-7.39 (4H, m) 7.45-7.56 (4H, m) 7.75 (1H, d, J = 6.9 Hz) 7.86 (1H, d, J = 7.4 Hz) 8.21 (1H, d, J = 8.2 Hz) 291 CD₃OD 270 2.22 (3H, s) 2.88-3.06 (1H, m) 3.11-3.19 (1H, m) 3.94 (3H, s) 4.22 (2H, s) 4.65 (1H, t, J = 8.0 Hz) 4.88 (4H, S) 6.55 (1h, S) 6.94-7.06 (3H, m) 7.24-7.27 (2H, m) 7.72-7.76 (2H, m) 292 CD₃OD 270 2.32 (3H, s) 2.79 (2H, s) 4.03-4.09 (2H, m) 4.88-4.94 (6H, m) 6.47 (2H, s) 6.78-6.81 (3H, s) 6.91-7.08 (2H, m) 7.16-7.53 (6H, m) 7.72-7.75 (1H, m) 7.83-7.85 (1H, m) 8.18 (1H, s) 293 CD₃OD 270 2.33 (3H, s) 3.30-3.48 (3H, m) 4.03-4.14 (2H, m) 4.83-4.91 (5H, m) 6.82 (1H, s) 7.17-7.20 (2H, m) 7.31-7.56 (8H, m) 7.83-7.88 (2H, m) 11.06 (1H, br s) 294 CD₃OD 270 1.27-1.37 (5H, m) 2.32 (2H, s) 3.13-3.15 (1H, m) 3.17-3.23 (3H, m) 4.20 (1H, s) 4.30 (1H, s) 6.91 (1H, d, J = 3.7 Hz) 6.94-7.07 (1H, m) 7.16-7.25 (8H, m) 7.53 (1H, d, J = 8.2 Hz) 7.71-7.73 (1H, m) 295 CD₃OD 270 1.32-1.36 (2H, m) 2.30 (3H, s) 3.20-3.38 (2H, m) 4.16 (1H, s) 4.82-4.85 (1H, m) 4.92 (4H, br s) 6.45 (1H, d, J = 3.9 Hz) 6.85-6.90 (2H, m) 7.12-7.35 (6H, m) 7.50 (2H, d, J = 7.9 Hz) 7.62-7.71 (2H, m) 296 CD₃OD 270 1.33-1.37 (1H, m) 2.33 (3H, s) 3.01-3.20 (2H, m) 3.30 (1H, s) 4.11-4.26 (2H, m) 4.70 (1H, t, J = 7.7 Hz) 4.91 (3H, s) 6.46 (1H, d, J = 3.9 Hz) 6.90-6.94 (2H, m) 7.17-7.25 (3H, m) 7.35-7.40 (2H, m) 7.53 (2H, d, J = 7.9 Hz) 7.68-7.70 (2H, m) 297 CD₃OD 270 1.27-1.32 (1H, m) 2.32 (3H, s) 3.07-3.17 (3H, m) 4.17 (2H, d, J = 4.5 Hz) 4.69-4.72 (1H, m) 4.91 (2H, s) 6.46 (1H, s) 6.88-6.91 (2H, m) 7.16-7.26 (5H, m) 7.50-7.53 (2H, m) 7.65-7.69 (2H, m) 8.61 (1H, d, J = 4.9 Hz) 11.03 (1H, s) 298 CD₃OD 270 3.29-3.31 (1H, m), 3.58-3.73 (1H, m), 4.05-4.13 (2H, m), 4.89-4.91 (4H, m), 6.83 (1H, d, J = 9.1 Hz), 7.06-7.09 (1H, m), 7.15 (1H, s), 7.19-7.25 (1H, m), 7.34-7.62 (9H, m), 7.73-7.76 (1H, m), 7.84-7.88 (1H, m), 8.22 (1H, d, J = 7.6 Hz), 8.40-8.60 (1H, m) 299 CD₃OD 270 3.61-3.71 (2H, m), 4.06-4.143 (2H, m), 4.90-4.97 (4H, m), 6.84 (1H, d, J = 9.1 Hz), 7.33-7.40 (4H, m), 7.49-7.55 (4H, m), 7.64-7.68 (2H, m), 7.74-7.77 (1H, m), 7.84-7.88 (1H, m), 8.26 (1H, d, J = 8.46 Hz), 8.40-8.60 (1H, m) 300 CD₃OD 270 3.57-3.60 (1H, m), 3.67-3.71 (1H, m), 3.72 (3H, s), 4.05-4.13 (2H, m), 4.86-4.92 (4H, m), 6.81-6.91 (2H, m), 7.07 (1H, s), 7.29-7.33 (3H, m), 7.37-7.54 (6H, m), 7.73-7.77 (1H, m), 7.85-7.88 (1H, m), 8.22 (1H, d, J = 8.2 Hz), 8.45-8.47 (1H, m) 301 CD₃OD 270 3.57-3.60 (1H, m), 3.707-3.73 (1H, m), 4.06-4.13 (2H, m), 4.86-4.92 (4H, m), 6.82 (1H, d, J = 9.1 Hz), 6.98-7.05 (1H, m), 7.12 (1H, s), 7.26-7.33 (3H, m), 7.36-7.55 (6H, m), 7.74-7.77 (1H, m), 7.85-7.88 (1H, m), 8.22 (1H, d, J = 8.2 Hz), 8.45-8.47 (1H, m) 302 CD₃OD 270 3.56-3.59 (1H, m), 3.69-3.72 (1H, m), 4.05-4.13 (2H, m), 4.86-4.90 (6H, m), 6.78-6.84 (2H, m), 6.95-6.99 (2H, m), 7.23-7.27 (1H, m), 7.31-7.40 (2H, m), 7.48-7.54 (4H, m), 7.74-7.77 (1H, m), 7.85-7.88 (1H, m), 8.21 (1H, d, J = 8.2 Hz), 8.45-8.47 (1H, m) 303 CD₃OD 270 2.1 (1H, s), 2.4 (2H, s), 2.6 (2H, s), 3.0-3.3 (2H, m), 4.1-4.2 (2H, m), 4.7-4.8 (1H, m), 6.6 (1H, m), 7.0-7.1 (1H, m), 7.2-7.3 (6H, m), 7.6-7.8 (4H, m), 8.8-8.9 (2H, m), 11.6 (1H, s) 304 CD₃OD 270 2.0 (3H, s), 3.4-3.7 (3H, m), 3.8 (3H, s), 4.1-4.3 (2H, m), 4.8-5.2 (3H, m), 5.5 (1H, s), 6.2-6.3 (1H, m), 6.8-6.9 (1H, m), 7.0-7.1 (3H, m), 7.2-7.4 (3H, m), 7.4-7.6 (3H, m), 7.8-7.9 (2H, m), 8.3 (1H, m) 305 CD₃OD 270 2.17 (3H, s), 3.55-3.58 (1H, m), 3.65-3.68 (1H, m), 3.96-3.98 (1H, m), 4.115-4.13 (1H, m), 4.89-4.95 (4H, m), 6.63 (1H, d, J = 9.1 Hz), 6.98-6.84 (2H, m), 6.98-7.05 (1H, m), 7.13 (1H, s), 7.26-7.52 (6H, m), 7.74-7.76 (1H, m), 7.84-7.88 (1H, m), 8.17-8.19 (1H, m), 8.45-8.47 (1H, m) 306 CD₃OD 270 3.40-3.60 (1H, m), 3.70-3.80 (1H, m), 3.89 (3H, d, J = 2.8 Hz), 4.05-4.11 (2H, m), 4.13-4.16 (1H, m), 4.89-4.91 (2H, m), 6.85 (1H, d, J = 8.9 Hz), 7.03 (1H, s), 7.07-7.12 (1H, m), 7.26-7.64 (9H, m), 7.76-7.78 (1H, m), 7.85-7.88 (1H, m), 8.22 (1H, d, J = 7.6 Hz), 8.50-8.59 (1H, m) 307 CD₃OD 270 3.05-3.10 (1H, m), 3.25-3.40 (2H, m), 4.10-4.25 (2H, m), 4.85-4.95 (1H, m), 4.95-5.10 (4H, m), 6.50 (1H, d, J = 8.15 Hz), 7.00-7.80 (11H, m) 308 CD₃OD 270 3.05-3.20 (1H, m), 3.25-3.40 (2H, m), 3.80 (3H, s), 4.10-4.25 (2H, m), 4.75-4.85 (1H, m), 4.95-5.05 (4H, m), 6.45-6.55 (1H, m), 6.85-6.90 (1H, m), 7.00-7.10 (2H, m), 7.25-7.80 (7H, m) 309 CD₃OD 270 1.7-1.8 (3H, m), 2.1-2.2 (3H, s), 4.1-4.2 (2H, m), 4.3 (1H, s), 4.8-5.0 (1H, m), 6.1-6.2 (1H, d, J = 7 Hz), 6.5-6.6 (1H, m), 7.0 (1H, s), 7.1-7.7 (10H, m), 9.4-9.5 (1H, m) 310 CD₃OD 270 1.2-1.3 (2H, m), 1.8-2.1 (3H, m), 2.2-2.3 (2H, m), 3.2-3.3 (2H, m), 3.8 (3H, s), 4.1-4.2 (2H, m), 4.8-4.9 (1H, m), 6.1-6.2 (1H, m) 7.1-7.4 (10H, m) 311 CD₃OD 270 3.00-3.40 (3H, m), 4.10-4.30 (2H, m), 4.70-4.80 (1H, m), 4.90-5.10 (3H, m), 6.80-7.80 (12H, m), 8.60-8.80 (1H, m) 312 CD₃OD 270 3.00-3.40 (4H, m), 3.80 (3H, s), 4.15-4.30 (2H, m), 4.75-4.90 (1H, m), 4.95-5.10 (2H, m), 6.80-7.40 (9H, m), 7.60-7.80 (2H, m), 8.40-8.70 (1H, m) 313 CD₃OD 270 3.00-3.40 (4H, m), 4.10-4.30 (2H, m), 4.80-4.90 (1H, m), 4.95-5.10 (3H, m), 6.90-7.80 (12H, m), 8.60-8.80 (1H, m), 10.90-11.10 (1H, m) 314 CD₃OD 270 3.05-3.40 (4H, m), 3.80 (3H, s), 4.10-4.30 (2H, m), 4.70-4.90 (1H, m), 4.95-5.10 (2H, m), 6.80-7.40 (9H, m), 7.60-7.80 (2H, m), 8.60-8.75 (1H, m) 315 d6- 270 2.1 (2H, s), 2.4 (2H, s), 2.6 (3H, s), 3.0-3.3 (2H, DMSO m), 4.2-4.3 (2H, m), 4.8 (1H, br s), 6.8 (1H, br m), 7.0-7.1 (1H, m), 7.1 (6H, m), 7.6-7.8 (2H, m), 8.8-8.9 (1H, m), 11.4 (1H, m) 316 CD₃OD 270 2.4 (3H, s), 2.6 (3H, s), 2.9-3.2 (2H, m), 4.1-4.2 (2H, m), 4.6-4.7 (1H, s), 6.8-6.9 (1H, m), 7.1-7.4 (8H, m), 8.2-8.3 (3H, m), 8.8 (2H, s), 11.4 (1H, s) 317 CD₃OD 270 2.69 (3H, s), 3.00-3.25 (2H, m), 3.28-3.35 (1H, m), 4.15-4.30 (2H, m), 4.65-4.80 (1H, m), 4.90-5.10 (3H, m), 6.85-7.70 (12H, m), 8.55-8.70 (1H, m) 318 CD₃OD 270 2.27 (3H, s) 3.00-3.25 (2H, m), 3.28-3.35 (1H, m), 3.80 (3H, s) 4.10-4.30 (2H, m), 4.75-4.85 (1H, m), 4.90-5.10 (4H, m), 6.80-7.50 (9H, m), 7.60-7.70 (2H, m), 8.50-8.70 (1H, m) 319 CD₃OD 270 2.2 (3H, s), 2.4 (3H, s), 3.0-3.2 (2H, m), 3.2-3.4 (3H, m), 4.0-4.3 (2H, m), 4.7-4.8 (1H, m), 6.7-6.8 (1H, m), 7.0-7.3 (8H, m), 7.4-7.5 (1H, m), 7.6-7.7 (2H, m), 8.4-8.6 (1H, m) 320 CD₃OD 270 2.4 (3H, s), 3.0-3.2 (3H, m), 3.3 (3H, s), 4.0-4.2 (2H, m), 4.7-4.8 (1H, m), 6.7 (1H, d, J = 7 Hz), 7.0-7.2 (4H, m), 7.3-7.5 (3H, m), 7.6-7.8 (2H, m), 8.6-8.7 (1H, m) 321 CD₃OD 270 2.4 (3H, s), 3.0-3.2 (2H, m), 3.3-3.5 (3H, s), 3.7 (3H, s), 4.0-4.4 (2H, m), 4.8-4.9 (2H, m), 6.6-6.8 (1H, m), 6.9-7.0 (1H, m), 7.1 (2H, s), 7.2-7.6 (4H, m), 7.7-7.8 (1H, m), 8.7-8.6 (1H, m) 322 d6- 270 2.38 (3H, s) 3.39-3.44 (2H, m) 4.12 (2H, s) DMSO 4.79 (1H, d, J = 4.9 Hz) 6.76 (1H, d, J = 8.7 Hz) 7.04-7.07 (1H, m) 7.18-7.26 (2H, m) 7.37-7.50 (4H, m) 7.62-7.72 (3H, m) 7.93 (2H, br s) 8.59 (1H, s) 8.83 (1H, d, J = 7.9 Hz) 11.54 (1H, br s) 324 CD₃OD 270 3.10-3.15 (1H, m) 3.22-3.30 (2H, m) 4.21 (2H, s) 4.78 (1H, t, J = 7.7 Hz) 4.92 (4H, s) 6.91 (1H, d, J = 8.4 Hz) 7.05-7.24 (5H, m) 7.41 (1H, d, J = 8.4 Hz) 7.58 (1H, d, J = 7.9 Hz) 7.71-7.78 (2H, m) 325 CD₃OD 270 3.12-3.33 (2H, m) 4.24 (1H, s) 4.76 (1H, s) 4.93 (6H, s) 7.10-7.24 (7H, m) 7.43 (1H, s) 7.62 (1H, s) 7.74-7.78 (2H, m) 326 CD₃OD 270 3.09-3.30 (2H, m) 4.21 (2H, s) 4.71-4.76 (1H, s) 4.91 (5H, s) 6.91-7.10 (7H, m) 7.72 (2H, s) 8.68 (1H, s) 327 CD₃OD 270 1.36 (1H, s) 3.03-3.30 (2H, m) 3.79 (3H, s) 4.19 (2H, s) 4.70-4.76 (1H, m) 4.91 (4H, s) 6.88-7.27 (8H, m) 7.69 (2H, s) 328 CD₃OD 270 3.11-3.21 (2H, m) 4.23 (2H, s) 4.73-4.79 (1H, t) 4.98 (5H, s) 6.93-7.16 (4H, m) 7.74-7.99 (4H, m) 8.26 (1H, s) 9.33 (1H, s) 329 d6- 270 3.0-3.2 (1H, m) 3.3-3.4 (2H, m), 4.0-4.2 (3H, DMSO m), 4.8-4.9 (1H, m), 7-7.8 (8H, m), 8.0-8.1 (1H, m), 8.7-9.0 (2H, m) 330 CD₃OD 270 3.12-3.19 (2H, m) 4.18 (2H, s) 4.73 (1H, br s) 4.91 (5H, s) 6.95-7.26 (8H, m) 7.60-7.66 (3H, m) 8.64 (1H, br s) 331 CD₃OD 270 3.09-3.30 (3H, m) 4.20 (2H, s) 4.71 (1H, br s) 4.89 (4H, br s) 6.96-7.10 (5H, m) 7.27-7.40 (4H, m) 7.69 (2H, s) 332 CD₃OD 270 3.09-3.30 (3H, m) 3.79 (3H, s) 4.19 (2H, s) 4.71 (1H, brs) 4.91 (4H, s) 6.91-7.05 (7H, m) 7.27-7.28 (2H, m) 7.67 (2H, s) 333 CD₃OD 270 4.09-4.18 (2H, m) 5.19 (2H, s) 5.70-5.75 (1H, m) 5.98 (5H, s) 7.89-7.97 (3H, m) 8.23-8.25 (2H, m) 8.85-9.00 (4H, m) 9.22 (1H, s) 10.34 (1H, s) 334 d6- 270 2.5 (3H, s), 2.9-3.1 (2H, m), 3.7 (3H, s), DMSO 4.1-4.2 (2H, m), 4.5-4.6 (1H, m), 6.77-6.8 (1H, d, J = 8 Hz), 6.9-6.93 (1H, d, J = 9 Hz), 7.00-7.06 (1H, m), 7.14-7.3 (4H, m), 7.38-7.41 (1H, d, J = 8 Hz), 7.6-7.65 (1H, d, J = 8 Hz), 7.7-7.71 (1H, m), 7.91-8.0 (1H, m), 8.7-8.8 (1H, m), 11.5 (1H, s) 335 d6- 270 3.39 (7H, s) 4.19 (1H, s) 4.85 (1H, s) DMSO 6.91-7.02 (2H, m) 7.18-7.23 (4H, m) 7.40-7.53 (4H, m) 7.80-8.01 (2H, m) 8.77 (1H, s) 11.52 (1H, s) 336 CD₃OD 270 1.3-1.6 (1H, m), 2.2-2.3 (3H, m), 2.8-2.9 (1H, m), 3.2-3.4 (6H, m), 4.0-4.4 (2H, m), 4.7-4.9 (1H, m), 6.5-6.6 (1H, m), 7.0-7.3 (6H, m), 7.4-7.6 (4H, m), 7.7-7.9 (1H, m) 337 CD₃OD 270 2.2 (3H, s), 3.3-3.4 (6H, m), 3.8 (3H, s), 3.9-4.2 (2H, m), 4.8-5.0 (1H, m), 6.5-6.6 (1H, d, J = Hz), 6.9-7.0 (3, m), 7.1-7.2 (4H, m), 7.3-7.5 (3H, m), 7.6-7.8 (1H, m), 8.3-8.4 (1H, m) 338 CD₃OD 270 1.1-1.0 (2H, m), 1.5-1.8 (10H, m), 2.5 (3H, s), 4.1-4.2 (2H, m), 4.5-4.6 (1H, m), 6.9-7.1 (2H, m), 7.2-7.3 (2H, m), 7.4-7.5 (1H, m), 7.6-7.7 (1H, m), 7.8-7.9 (1H, m), 8.0-8.1 (1H, s), 8.5-8.7 (2H, m), 11.6 (1H, s) 339 CD₃OD 400 0.99-1.14 (10H, m), 1.22-1.39 (6H, m), 1.65-1.84 (9H, m), 1.98-2.09 (2H, m), 2.71 (3H, s), 4.24-4.44 (2H, m), 4.53 (1H, dd, J = 6.64, 8.8 Hz), 7.06 (1H, d, J = 9.16 Hz) 7.85 (1H, s), 7.95 (1H, dd, J = 1.96, 9.12 Hz), 8.79-8.82 (1H, m) 340 CD₃OD 400 0.58-0.89 (5H, m) 1.15-1.25 (3H, m) 1.88-1.99 (1H, m) 2.51-2.54 (3H, m) 2.76-2.88 (2H, m) 3.01-3.22 (3H, m) 3.47-3.55 (1H, m) 4.11-4.21 (1H, m) 4.52-4.64 (1H, m) 6.87 (1H, d, J = 8.0 Hz) 7.05-7.19 (1H, m) 7.31-7.48 (2H, m) 7.65-7.77 (2H, m) 8.66 (1H, d, J = 4.0 Hz) 341 CD₃OD 400 0.70 (3H, d, J = 8.0 Hz) 0.76 (3H, d, J = 8.0 Hz) 1.88-1.96 (1H, m) 2.46-2.54 (3H, m) 2.80-2.92 (1H, m) 3.03-3.17 (2H, m) 3.20-3.22 (1H, m) 3.49 (1H, t, J = 4.0 Hz) 4.12-4.16 (2H, m) 4.53-4.57 (1H, m) 4.77 (3H, br s) 6.89 (1H, d, J = 8.0 Hz) 7.10-7.22 (4H, m) 7.60 (1H, d, J = 4.0 Hz) 7.68 (1H, dd, J = 8.0, 4.0 Hz) 342 CD₃OD 400 2.53 (3H, s) 2.55-2.62 (1H, m) 2.71-2.77 (1H, m) 2.93-3.01 (2H, m) 3.95 (1H, t, J = 4.0 Hz) 4.09 (2H, d, J = 4.0 Hz) 4.34 (1H, t, J = 4.0 Hz) 4.82 (5H, br s) 6.83 (1H, dd, J = 8.0, 4.0 Hz) 6.92-6.99 (3H, m) 7.04 (1H, s) 7.09-7.20 (5H, m) 7.58-7.61 (2H, m) 343 CD₃OD 400 0.76-0.93 (2H, m), 1.15-1.38 (3H, m), 1.54 (3H, d, J = 6.6 Hz), 1.71-1.86 (6H, m), 2.41 (1H, br s), 2.83 (3H, s), 2.90-2.94 (2H, m), 3.09-3.14 (1H, m), 3.88 (1H, br s), 4.18-4.30 (2H, m), 4.63-4.68 (1H, m), 6.97 (1H, d, J = 9.1 Hz), 7.05-7.08 (1H, m), 7.14-7.21 (2H, m), 7.73 (1H, s), 7.78 (1H, d, J = 9.2 Hz), 8.70-8.73 (1H, m). 344 CD₃OD 400 1.58 (3H, d, J = 8.9 Hz), 2.83 (6H, s), 2.90-3.05 (1H, m), 3.10-3.21 (1H, m), 3.90 (1H, q, J = 7 Hz), 4.18-4.23 (1H, m), 4.28-4.39 (1H, m), 4.67 (1H, t, J = 7.6 Hz), 4.91 (3H, s), 7.00 (1H, d, J = 9.0 Hz), 7.08-7.10 (1H, m), 7.16-7.30 (2H, m), 7.77 (1H, d, J = 3.96 Hz), 7.80 (1H, t, J = 7.04 Hz), 8.72-8.74 (1H, m). 345 CD₃OD 400 1.26 (3H, t, J = 7.2 Hz), 1.53 (3H, d, J = 7.0 Hz), 2.78 (3H, s), 2.93-3.13 (4H, m), 3.89-3.94 (1H, m), 4.16-4.29 (2H, m), 4.63-4.67 (1H, m), 6.96 (1H, d, J = 9.1 Hz), 7.03-7.06 (1H, m), 7.10-7.20 (2H, m), 7.73 (1H, s), 7.76 (1H, dd, J = 9.2, 2.1 Hz), 8.70 (1H, t, J = 5.9 Hz). 346 CD₃OD 400 0.92-0.99 (3H, m), 1.54 (3H, d, J = 7.0 Hz), 1.66-1.72 (2H, m), 2.80 (3H, s), 2.93-3.13 (4H, m), 3.90-3.99 (1H, m), 4.16-4.29 (2H, m), 4.62-4.66 (1H, m), 6.96 (1H, d, J = 9.1 Hz), 7.03-7.06 (1H, m), 7.11-7.20 (2H, m), 7.73 (1H, s), 7.77 (1H, dd, J = 9.1, 2.0 Hz), 8.71 (1H, t, J = 5.8 Hz). 347 CD₃OD 400 0.94-0.97 (3H, m), 1.54 (3H, d, J = 7.0 Hz), 1.60-1.68 (2H, m), 2.80 (3H, s), 2.82-3.13 (6H, m), 3.91-3.96 (1H, m), 4.16-4.29 (2H, m), 4.62-4.66 (1H, m), 6.96 (1H, d, J = 9.2 Hz), 7.03-7.06 (1H, m), 7.11-7.20 (2H, m), 7.73 (1H, s), 7.74-7.78 (1H, m), 8.71 (1H, t, J = 5.9 Hz). 348 CD₃OD 400 0.99-1.20 (9H, m), 1.30 (3H, d, J = 6.6 Hz), 1.39 (1H, s), 2.41 (1H, s), 2.60-2.70 (3H, m), 2.79-2.84 (1H, m), 2.95-3.01 (1H, m), 3.15-3.20 (1H, m), 3.81 (1H, s), 4.22-4.33 (2H, m), 7.02 (1H, d, J = 9.1 Hz), 7.06-7.09 (1H, m), 7.21-7.28 (2H, m), 7.80-7.83 (2H, m), 8.79-8.82 (1H, m). 349 CD₃OD 400 0.98-1.05 (6H, m), 1.11-1.24 (3H, m), 1.30 (3H, d, J = 6.6 Hz), 1.37-1.40 (1H, m), 1.63 (1H, s), 2.07-2.09 (1H, m), 2.56-2.69 (3H, m), 2.83-2.86 (1H, m), 2.96-3.01 (1H, m), 3.14-3.19 (1H, m), 3.81-3.82 (1H, m), 4.22-4.33 (2H, m), 7.02 (1H, d, J = 9.1 Hz), 7.11-7.14 (1H, m), 7.21-7.28 (2H, m), 7.80-7.85 (2H, m), 8.80 (1H, s). 350 CD₃OD 400 1.04-1.17 (6H, m) 1.30-1.47 (6H, m) 1.53 (3H, d, J = 8.0 Hz) 2.94-3.04 (2H, m) 3.07-3.17 (1H, m) 3.34-3.47 (1H, m) 3.90-4.06 (2H, m) 4.20 (1H, dd, J = 8.0, 4.0 Hz) 4.31-4.41 (1H, m) 4.63-4.78 (1H, m) 4.91-5.01 (2H, br m) 7.00-7.08 (1H, m) 7.11-7.17 (1H, m) 7.19-7.32 (2H, m) 7.74-7.77 (2H, m) 8.78 (1H, t, J = 4.0 Hz) 351 CD₃OD 400 2.88-2.92 (7H, m), 2.99-3.04 (1H, m), 3.11-3.17 (1H, m), 3.39-3.42 (1H, m), 4.03-4.11 (2H, m), 4.16-4.22 (1H, m), 4.59 (1H, t, J = 7.8 Hz), 6.99-7.04 (2H, m), 7.10-7.35 (7H, m), 7.69-7.70 (1H, m), 7.72 (1H, s), 8.29 (1H, t, J = 5.8 Hz). 352 CD₃OD 400 1.33 (3H, t, J = 6.9 Hz), 2.84-3.21 (9H, m), 4.03-4.23 (3H, m), 4.59-4.63 (1H, m), 6.99-7.05 (2H, m), 7.11-7.35 (7H, m), 7.70-7.71 (1H, m), 7.73 (1H, s), 8.30 (1H, t, J = 5.8 Hz). 353 CD₃OD 400 0.98-1.05 (6H, m), 1.11-1.24 (3H, m), 1.30 (3H, d, J = 6.6 Hz), 1.37-1.40 (1H, m), 1.63 (1H, s), 2.07-2.09 (1H, m), 2.56-2.69 (3H, m), 2.83-2.86 (1H, m), 2.96-3.01 (1H, m), 3.14-3.19 (1H, m), 3.81-3.82 (1H, m), 4.22-4.33 (2H, m), 7.02 (1H, d, J = 9.1 Hz), 7.11-7.14 (1H, m), 7.21-7.28 (2H, m), 7.80-7.85 (2H, m), 8.80 (1H, s). 354 CD₃OD 400 1.31 (2H, d, J = 8.0 Hz) 1.41 (2H, d, J = 8.0 Hz) 1.52-1.84 (6H, br m) 2.76-2.87 (3H, m) 2.93-3.08 (2H, m) 3.12-3.25 (1H, m) 3.45 (1H, br s) 3.67-3.79 (1H, m) 4.10-4.23 (2H, m) 4.45-4.49 (1H, m) 4.55-4.61 (1H, m) 6.86 (1H, d, J = 8.0 Hz) 6.90-6.95 (1H, m) 7.01-7.12 (2H, m) 7.57-7.68 (2H, m 08.64 (1H, t, J = 4.0 Hz) 355 CD₃OD 400 1.28-1.49 (6H, m) 1.56 (3H, d, J = 8.0 Hz) 2.93-3.03 (2H, m) 3.14-3.29 (3H, m) 3.36-3.37 (1H, m) 4.04 (1H, q, J = 8.0 Hz) 4.23-4.33 (2H, m) 4.65 (1H, q, J = 8.0 Hz) 5.00 (3H, m) 7.02 (1H, d, J = 8.0 Hz) 7.10-7.12 (1H, m) 7.18-7.25 (2H, m) 7.78-7.84 (2H, m) 8.81 (1H, t, J = 4.0 Hz) 356 CD₃OD 400 1.22 (2H, d, J = 8.0 Hz) 1.36 (2H, d, J = 8.0 Hz) 1.91-1.93 (5H, br m) 2.71 (1H, br s) 2.78-2.88 (1H, m) 2.97-3.13 (3H, m) 3.21-3.24 (1H, m) 3.46 (1H, br s) 3.76-3.88 (1H, m) 4.07-4.15 (2H, m) 4.42-4.54 (1H, m) 4.83 (1H, s) 6.87 (1H, dd, J = 8.0, 4.0 Hz) 6.93-6.95 (1H, m) 7.02-7.08 (2H, m) 7.61-7.69 (2H, m) 357 CD₃OD 400 1.46 (2H, d, J = 8.0 Hz) 1.59 (2H, d, J = 8.0 Hz) 2.10 (5H, br s) 2.96-3.03 (1H, m) 3.11-3.16 (1H, m) 3.32-3.37 (5H, m) 3.87-3.96 (1H, m) 4.18-4.24 (1H, m) 4.30 (1H, s) 4.33 (1H, s) 4.63-4.70 (1H, m) 7.01 (1H, d, J = 8.0 Hz) 7.09 (1H, br s) 7.15-7.25 (2H, m) 7.77-7.83 (2H, m) 359 CD₃OD 400 0.90 (6H, dd, J = 2.22, 6.72 Hz) 2.09-2.42 (1H, m) 2.93 (6H, s) 2.97-3.03 (1H, m) 3.11-3.20 (1H, m) 3.66 (1H, d, J = 6.0 Hz) 4.28-4.31 (2H, m) 4.61-4.65 (1H, m) 4.92 (4H, br s) 7.02 (1H, d, J = 9.08 Hz), 7.11-7.15 (1H, m), 7.21-7.26 (2H, m) 7.81-7.86 (2H, m), 8.79-8.82 (1H, m) 360 CD₃OD 400 1.21 (3H, s), 1.27 (3H, d, J = 6.6 Hz), 2.78 (3H, s), 2.93-3.08 (2H, m), 3.23-3.28 (1H, m), 4.03-4.11 (3H, m), 4.25-4.41 (2H, m), 4.82 (1H, s), 7.02 (1H, d, J = 9.1 Hz), 7.11-7.14 (1H, m), 7.20-7.27 (2H, m), 7.79 (1H, d, J = 1.3 Hz), 7.85 (1H, dd, J = 9.2, 2.0 Hz), 8.72 (1H, t, J = 5.8 Hz). 361 CD₃OD 400 1.31 (3H, t, J = 7.3 Hz), 2.90 (3H, s), 2.96-3.01 (1H, m), 3.14-3.23 (3H, m), 4.00 (1H, t, J = 4.5 Hz), 4.05-4.12 (2H, m), 4.23-4.34 (2H, m), 4.73-4.77 (1H, m), 7.01 (1H, d, J = 9.1 Hz), 7.09-7.12 (1H, m), 7.19-7.25 (2H, m), 7.77 (1H, d, J = 1.2 Hz), 7.82 (1H, dd, J = 9.1, 2.1 Hz), 8.70 (1H, t, J = 5.8 Hz). 362 CD₃OD 400 1.26 (6H, t, J = 7.2 Hz), 2.95-3.01 (1H, m), 3.08-3.45 (5H, m), 4.03-4.09 (3H, m), 4.24-4.36 (2H, m), 4.75-4.79 (1H, m), 7.02 (1H, d, J = 9.2 Hz), 7.09-7.12 (1H, m), 7.19-7.26 (2H, m), 7.78 (1H, d, J = 1.2 Hz), 7.83 (1H, dd, J = 9.2, 2.1 Hz). 363 CD₃OD 400 1.36 (6H, t, J = 7.3 Hz), 3.01-3.15 (2H, m), 3.31-3.38 (4H, m), 3.92-4.01 (2H, m), 4.10-4.12 (1H, m), 4.19-4.33 (2H, m), 4.61 (1H, t, J = 7.7 Hz), 7.00-7.02 (1H, m), 7.06-7.09 (1H, m), 7.15-7.25 (2H, m), 7.78-7.81 (2H, m), 8.77 (1H, t, J = 5.8 Hz). 364 CD₃OD 400 1.26 (6H, t, J = 7.2 Hz), 1.37-1.43 (1H, m), 2.96-3.25 (7H, m), 3.76 (3H, s), 4.25-4.38 (3H, m), 4.75-4.79 (1H, m), 7.02 (1H, d, J = 9.5 Hz), 7.10-7.13 (1H, m), 7.20-7.28 (2H, m), 7.79 (1H, d, J = 1.7 Hz), 7.84 (1H, dd, J = 9.2, 2.2 Hz), 8.62 (1H, t, J = 5.8 Hz). 365 CD₃OD 400 1.07 (3H, d, J = 8.0 Hz) 1.25 (3H, d, J = 4.0 Hz) 1.33-1.40 (1H, m) 1.50-1.72 (4H, m) 1.79-1.94 (4H, m) 2.92-3.01 (1H, m) 3.16-3.21 (1H, m) 3.53-3.65 (2H, m) 3.78-3.93 (2H, m) 4.16-4.27 (2H, m) 4.72 (1H, q, J = 4.0 Hz) 7.02 (1H, d, J = 12.0 Hz) 7.10 (1H, br s) 7.17-7.23 (2H, m) 7.75-7.84 (2H, m) 8.82-8.87 (1H, m) 366 CD₃OD 400 2.09-2.12 (5H, m) 2.92-3.06 (2H, m) 3.12-3.20 (3H, m) 3.69-3.71 (3H, br m) 4.03-4.14 (2H, m) 4.26 (2H, s) 4.65 (1H, t, J = 8.0 Hz) 7.01 (2H, d, J = 8.0 Hz) 7.06-7.09 (1H, m) 7.15-7.26 (2H, m) 7.77-7.86 (2H, m) 367 CD₃OD 400 1.08-1.12 (3H, m), 1.39 (3H, d, J = 6.9 Hz), 2.61 (3H, s), 2.78-3.01 (4H, m), 3.74-3.79 (1H, m), 4.03-4.14 (2H, m), 4.52-4.58 (1H, m), 6.81-6.90 (3H, m), 7.10-7.15 (2H, m), 7.57 (1H, s), 7.61 (1H, dd, J = 9.2, 2.1 Hz), 8.56 (1H, t, J = 5.8 Hz). 368 CD₃OD 400 0.78-0.84 (3H, m), 1.39 (3H, d, J = 7.0 Hz), 1.52-1.56 (2H, m), 2.63 (3H, s), 2.68-3.00 (4H, m), 3.74-3.79 (1H, m), 4.02-4.17 (2H, m), 4.49-4.53 (1H, m), 6.80-6.88 (3H, m), 7.10-7.14 (2H, m), 7.56 (1H, s), 7.58-7.61 (1H, m), 8.71 (1H, t, J = 5.6 Hz). 369 CD₃OD 400 0.93-0.97 (3H, m), 1.32-1.40 (2H, m), 1.53 (3H, d, J = 6.9 Hz), 1.61-1.70 (2H, m), 2.78 (3H, s), 2.83-3.14 (4H, m), 3.90-3.98 (1H, m), 4.17-4.28 (2H, m), 4.63-4.67 (1H, m), 6.95-7.02 (3H, m), 7.19-7.28 (2H, m), 7.71 (1H, s), 7.74 (1H, dd, J = 9.2, 2.0 Hz), 8.69 (1H, t, J = 5.7 Hz). 370 CD₃OD 400 0.99-1.13 (9H, m), 1.27 (3H, d, J = 6.4 Hz), 1.37 (1H, s), 2.40-2.53 (2H, m), 2.68 (3H, s), 2.94-3.00 (1H, m), 3.16-3.21 (1H, m), 3.78-3.79 (1H, m), 4.27-4.38 (2H, m), 7.01 (1H, d, J = 9.2 Hz), 7.07 (2H, t, J = 8.6 Hz), 7.32-7.36 (2H, m), 7.79-7.84 (2H, m), 8.81-8.89 (1H, m). 371 CD₃OD 400 0.98 (3H, d, J = 6.4 Hz), 1.03 (3H, t, J = 7.2 Hz), 1.15 (3H, d, J = 6.2 Hz), 1.27 (3H, d, J = 6.4 Hz), 1.36-1.39 (1H, m), 1.58-1.63 (1H, m), 2.05-2.13 (1H, m), 2.46-2.49 (1H, m), 2.67 (3H, s), 2.71-2.75 (1H, m), 2.94-3.00 (1H, m), 3.15-3.20 (1H, m), 3.79 (1H, s), 4.27-4.36 (2H, m), 7.01 (1H, d, J = 9.2 Hz), 7.07 (2H, t, J = 8.4 Hz), 7.32-7.35 (2H, m), 7.79-7.84 (2H, m), 8.80 (1H, s). 372 CD₃OD 400 1.16-1.33 (6H, m) 1.38 (6H, d, J = 8.0 Hz) 1.57 (3H, d, J = 8.0 Hz) 2.87-3.00 (2H, m) 3.13-3.18 (1H, m) 3.31-3.37 (1H, m) 3.96-4.05 (2H, m) 4.21 (1H, d, J = 12.0, 4.0 Hz) 4.34-4.48 (1H, m) 4.72-4.79 (1H, m) 4.96-5.06 (2H, br m) 7.00-7.07 (3H, m) 7.28-7.32 (2H, m) 7.71-7.74 (2H, m) 8.76 (1H, t, J = 4.0 Hz) 373 CD₃OD 400 1.19-1.26 (6H, m), 2.79-2.85 (5H, m), 3.00-3.08 (2H, m), 3.41-3.45 (1H, m), 4.03-4.08 (1H, m), 4.14-4.21 (2H, m), 4.70 (1H, s), 7.00-7.05 (3H, m), 7.23-7.34 (7H, m), 7.71-7.74 (2H, m), 8.16-8.19 (1H, m), 8.69 (1H, d, J = 8.6 Hz). 374 CD₃OD 400 1.43 (3H, d, J = 8.0 Hz) 1.54-1.57 (1H, m) 1.85-1.99 (5H, m) 2.97-3.03 (3H, m) 3.12-3.17 (1H, m) 3.36-3.41 (2H, M) 3.60 (1h, D, j = 8.0 Hz) 3.90 (1H, q, J = 8.0 Hz) 4.21-4.31 (2H, m) 4.60-4.64 (1H, m) 5.02-5.07 (2H, m) 6.92-7.08 (3H, m) 7.28-7.31 (2H, m) 7.77-7.80 (2H, m) 8.77 (1H, t, J = 4.0 Hz) 375 CD₃OD 400 1.40 (4H, d, J = 8.0 Hz) 1.51-1.57 (1H, m) 1.68 (3H, d, J = 12.0 Hz) 1.77-1.81 (1H, m) 2.57-2.71 (2H, m) 2.78-2.87 (2H, m) 3.00-3.05 (1H, m) 3.20-3.22 (1H, m) 3.40 (1H, d, J = 4.0 Hz) 3.61-3.69 (1H, m) 4.07-4.18 (2H, m) 4.58-4.62 (1H, m) 4.81 (2H, br s) 6.84-6.93 (3H, m) 7.14-7.18 (2H, m) 7.61-7.66 (2H, m) 8.62 (1H, t, J = 4.0 Hz) 376 CD₃OD 400 1.23-1.29 (6H, m) 1.55 (3H, d, J = 8.0 Hz) 2.78 (1H, br s) 2.87-3.04 (2H, m) 3.16-3.21 (2H, m) 3.32-3.34 (1H, m) 4.02 (1H, q, J = 8.0 Hz) 4.28 (2H, d, J = 4.0 Hz) 4.74 (1H, q, J = 8.0 Hz) 5.03 (4H, br s) 7.03-7.15 (3H, m) 7.25-7.37 (2H, m) 7.71-7.81 (2H, m) 377 CD₃OD 400 0.70-0.78 (1H, m) 0.86-0.91 (6H, m) 1.24-1.32 (1H, m) 2.01-2.07 (1H, m) 2.92 (6H, m) 2.97-3.03 (1H, m) 3.21-3.27 (1H, m) 3.72 (1H, d, J = 8.0 Hz) 4.23-4.44 (2H, m) 4.64-4.72 (1H, m) 4.95 (3H, s) 6.96-7.04 (2H, m) 7.09 (1H, d, J = 8.0 Hz) 7.17 (1H, d, J = 8.0 Hz) 7.34-7.39 (1H, m) 7.80 (1H, s) 7.86 (1H, dd, J = 8.0, 4.0 Hz) 8.84-8.92 (1H, m) 378 CD₃OD 400 1.05 (2H, d, J = 8.0 Hz) 1.22-1.32 (4H, m) 1.45-1.50 (2H, m) 1.61-1.68 (1H, m) 1.78-1.95 (3H, m) 2.95-3.01 (1H, m) 3.16-3.21 (1H, m) 3.50-3.55 (2H, m) 3.77-3.92 (2H, m) 4.26 (2H, s) 4.71 (1H, q, J = 8.0 Hz) 4.94 (4H, s) 6.99-7.05 (3H, m) 7.28-7.36 (2H, m) 7.76-7.81 (2H, m) 379 CD₃OD 400 1.56 (1H, s) 1.88 (6H, s) 2.88-3.00 (3H, m) 3.14-3.24 (1H, m) 3.34-3.37 (1H, m) 3.50 (1H, br s) 3.87-3.99 (2H, m) 4.26 (2H, s) 4.66-4.72 (2H, m) 5.02 (2H, s) 6.96-7.02 (3H, m) 7.27-7.30 (2H, m) 7.75-7.80 (2H, m) 380 CD₃OD 400 1.34-1.41 (6H, m) 2.95-3.01 (1H, m) 3.14-3.33 (5H, m) 3.37-3.40 (1H, m) 3.92-4.08 (2H, m) 4.21-4.39 (2H, m) 4.64-4.71 (1H, m) 4.86-4.92 (2H, m) 6.96-7.10 (3H, m) 7.27-7.31 (2H, m) 7.73-7.82 (2H, m) 8.73-8.76 (1H, m) 381 CD₃OD 400 0.96-1.06 (2H, m) 1.24-1.44 (10H, m) 1.52 (3H, d, J = 4.0 Hz) 1.79 (4H, d, J = 8.0 Hz) 2.79 (3H, s) 3.36-3.37 (1H, m) 3.55-3.58 (1H, m) 3.89 (1H, br s) 4.12 (1H, d, J = 8.0 Hz) 4.28-4.35 (2H, m) 4.40-4.50 (1H, m) 7.04 (1H, d, J = 8.0 Hz) 7.81 (1H, s) 7.92 (1H, dd, J = 8.0, 4.0 Hz) 8.83 (1H, t, J = 8.0 Hz) 382 CD₃OD 400 0.99-1.12 (2H, m), 1.14-1.42 (4H, m), 1.62-1.95 (7H, m), 2.07-2.28 (4H, m), 2.61-2.69 (1H, m), 2.93, 2.97 (3H, 2xs), 3.15-3.29 (3H, m), 3.75-3.89 (1H, m), 4.14-4.19 (1H, m), 4.31-4.37 (2H, m), 4.46 (1H, t, J = 7.7 Hz), 7.03 (1H, d, J = 9.24 Hz) 7.81 (1H, s), 7.92 (1H, dd, J = 9.24, 2.15 Hz) 8.78-8.81 (1H, m) 383 CD₃OD 400 0.88-1.08 (6H, m), 1.22-1.50 (5H, m), 1.62 (3H, d, J = 6.96 Hz), 1.64-1.69 (4H, m), 1.77-1.84 (8H, m), 2.94 (3H, s), 4.03 (1H, dd, J = 6.92, 13.81 Hz), 4.32-4.34 (2H, m), 4.47-4.53 (1H, m), 7.04 (1H, d, J = 9.09 Hz) 7.81 (1H, d, J = 1.05 Hz), 7.92 (1H, dd, J = 2.2, 9.28 Hz), 8.77-8.90 (1H, m) 384 CD₃OD 400 0.96-1.08 (2H, m), 1.19-1.36 (4H, m), 1.40 (3H, t, J = 7.3 Hz), 1.61 (3H, d, J = 6.9 Hz), 1.65-1.83 (7H, m), 2.92 (3H, s), 3.22-3.28 (2H, m), 4.05 (1H, q, d, J = 6.9 Hz), 4.28-4.40 (2H, m), 4.46-4.50 (1H, m), 7.04 (1H, d, J = 9.6 Hz), 7.81 (1H, s), 7.93 (1H, dd, J = 9.2, 2.2 Hz), 8.79 (1H, t, J = 5.7 Hz). 385 CD₃OD 400 0.99-1.00 (2H, m), 1.07 (6H, t, J = 7.24 Hz), 1.22-1.40 (6H, m), 1.61 (3H, d, J = 6.92 Hz), 1.66-1.87 (10H, m), 3.10-3.19 (2H, m, br), 3.21-3.28 (2H, m), 4.13 (1H, dd, J = 7.37, 13.84 Hz), 4.32 (2H, d, J = 5.72 Hz), 4.49 (1H, dd, J = 6.08, 9.2 Hz), 4.91 (2H, s), 7.04 (1H, d, J = 9.25 Hz) 7.81 (1H, s), 7.93 (1H, dd, J = 2.04, 9.16 Hz), 8.77-8.80 (1H, m) 386 CD₃OD 400 0.84-0.95 (2H, m), 1.08-1.29 (4H, m), 1.52-1.70 (7H, m), 2.88 (6H, s), 3.91 (1H, t, J = 4.3 Hz), 3.96-4.04 (2H, m), 4.14-4.24 (2H, m), 4.35-4.39 (1H, m), 6.89 (1H, d, J = 9.1 Hz), 7.66 (1H, d, J = 1.4 Hz), 7.77 (1H, dd, J = 9.2, 2.1 Hz), 8.59 (1H, t, J = 5.8 Hz). 387 CD₃OD 400 0.98-1.09 (2H, m), 1.19-1.33 (4H, m), 1.41 (3H, t, J = 7.3 Hz), 1.66-1.80 (7H, m), 3.00 (3H, s), 3.31-3.37 (2H, m), 4.10-4.17 (3H, m), 4.28-4.38 (2H, m), 4.49-4.53 (1H, m), 7.03 (1H, d, J = 9.4 Hz), 7.79 (1H, d, J = 1.2 Hz), 7.91 (1H, dd, J = 9.2, 2.2 Hz), 8.72 (1H, t, J = 5.8 Hz). 388 CD₃OD 400 0.99-1.10 (2H, m), 1.21-1.33 (4H, m), 1.39 (3H, d, J = 6.3 Hz), 1.44 (3H, d, J = 6.6 Hz), 1.63-1.84 (7H, m), 2.89 (3H, s), 3.67 (1H, br s), 4.06-4.16 (3H, m), 4.32 (2H, s), 4.51-4.55 (1H, m), 7.03 (1H, d, J = 9.1 Hz), 7.80 (1H, d, J = 1.4 Hz), 7.91 (1H, dd, J = 9.2, 2.1 Hz), 8.71 (1H, t, J = 5.8 Hz). 389 CD₃OD 400 0.95-1.10 (2H, m), 1.22-1.33 (4H, m), 1.40 (6H, t, J = 7.3 Hz), 1.63-1.84 (7H, m), 3.33-3.46 (4H, m), 4.07-4.19 (3H, m), 4.32 (2H, s), 4.50-4.54 (1H, m), 7.04 (1H, d, J = 9.0 Hz), 7.79 (1H, d, J = 1.4 Hz), 7.91 (1H, dd, J = 9.2, 2.1 Hz), 8.71 (1H, t, J = 5.8 Hz). 390 CD₃OD 400 0.96-1.09 (3H, m), 1.13-1.29 (4H, m), 1.38 (6H, d, J = 7.32 Hz), 1.60 (3H, d, J = 6.84 Hz), 1.65-1.83 (8H, m), 3.21-3.26 (2H, m), 4.08 (1H, dd, J = 6.92, 13.84 Hz), 4.32-4.38 (2H, m), 4.48-4.58 (1H, m), 4.91 (3H, s), 7.04 (1H, d, J = 9.05 Hz) 7.81 (1H, d, J = 1.05 Hz), 7.92 (1H, dd, J = 2.2, 9.28 Hz), 8.77-8.80 (1H, m) 391 CD₃OD 400 0.96-1.08 (3H, m), 1.22-1.40 (5H, m), 1.61 (3H, d, J = 6.96 Hz), 1.65-1.80 (7H, m), 2.95 (6H, s), 3.95-4.00 (1H, m), 4.32-4.38 (2H, m), 4.48-4.38 (1H, m), 4.46-4.54 (1H, m), 7.04 (1H, d, J = 9.09 Hz) 7.81 (1H, d, J = 1.36 Hz), 7.93 (1H, dd, J = 2.16, 9.28 Hz), 8.77-8.80 (1H, m) 392 CD₃OD 400 0.94-1.09 (2H, m), 1.21-1.41 (10H, m), 1.49-1.99 (16H, m), 3.57-3.58 (2H, m, br), 3.91 (2H, s), 4.31-4.37 (2H, m), 4.49-4.51 (1H, m), 7.04 (1H, d, J = 9.24 Hz) 7.81 (1H, d, J = 1.36 Hz), 7.92 (1H, dd, J = 2.07, 9.16 Hz), 8.82-8.83 (1H, m) 393 CD₃OD 400 0.94-1.08 (2H, m), 1.18-1.43 (16H, m), 1.65-1.83 (7H, m), 3.76-3.83 (2H, m), 4.02 (2H, s), 4.26-4.39 (2H, m), 4.47-4.52 (1H, m), 7.04 (1H, d, J = 9.1 Hz), 7.81 (1H, d, J = 1.4 Hz), 7.92 (1H, dd, J = 9.1, 2.1 Hz), 8.77 (1H, d, J = 7.2 Hz), 8.85 (1H, t, J = 5.8 Hz). 394 CD₃OD 400 1.13-1.85 (31H, m), 3.77-3.85 (2H, m), 3.97-4.03 (2H, m), 4.26-4.47 (3H, m), 7.03-7.05 (1H, m), 7.81 (1H, s), 7.92 (1H, dd, J = 9.2, 2.0 Hz), 8.71-8.91 (2H, m). 395 CD₃OD 400 1.18-1.86 (28H, m), 2.79 (3H, s), 3.56 (1H, s), 4.08-4.13 (1H, m), 4.32 (2H, s), 4.42-4.46 (1H, m), 7.04 (1H, d, J = 9.1 Hz), 7.81 (1H, s), 7.93 (1H, dd, J = 9.2, 2.1 Hz), 8.84-8.91 (1H, m). 396 CD₃OD 400 1.15-1.85 (19H, m), 2.04-2.12 (2H, m), 2.22-2.31 (1H, m), 2.63-2.72 (1H, m), 2.96-2.97 (3H, m), 3.25-3.32 (1H, m), 3.75-3.82 (1H, m), 4.19-4.45 (4H, m), 7.05 (1H, d, J = 9.1 Hz), 7.82 (1H, s), 7.91-7.95 (1H, m), 8.84-8.95 (1H, m). 397 CD₃OD 400 0.98-1.81 (19H, m), 3.04 (6H, s), 3.10-3.16 (1H, m), 3.41-3.45 (1H, m), 3.91-3.97 (1H, m), 4.07-4.13 (1H, m), 4.18-4.26 (1H, m), 4.39-4.43 (1H, m), 7.04 (1H, d, J = 9.1 Hz), 7.28-7.41 (5H, m), 7.84 (1H, s), 7.91 (1H, dd, J = 9.3, 2.0 Hz), 8.56-8.61 (1H, m) 8.79-8.81 (1H, m). 398 CD₃OD 400 0.53 (3H, d, J = 8.0 Hz) 0.62 (4H, t, J = 4.0 Hz) 1.33-1.43 (1H, m) 1.58-1.64 (1H, m) 2.11 (6H, s) 2.57 (2H, d, J = 8.0 Hz) 2.89-2.97 (1H, m) 3.21 (1H, quintet, J = 4.0 Hz) 4.07 (2H, s) 4.53 (1H, dd, J = 16.0, 4.0 Hz) 4.75 (3H, s) 6.43 (1H, d, J = 8.0 Hz) 7.00-7.08 (1H, m) 7.20-7.42 (3H, m) 7.70 (1H, d, J = 8.0 Hz) 399 CD₃OD 400 0.88-0.92 (6H, m) 2.31-2.42 (1H, m) 2.93 (6H, s) 2.98-3.04 (1H, m) 3.11-3.20 (1H, m) 3.65 (1H, d, J = 4.0 Hz) 4.29 (2H, s) 4.63-4.69 (1H, m) 4.96 (4H, br s) 7.02 (1H, dd, J = 8.0, 4.0 Hz) 7.27 (1H, dd, J = 8.0, 4.0 Hz) 7.35-7.49 (2H, m) 7.74-7.82 (2H, m) 400 CD₃OD 400 2.23 (6H, s) 2.28-2.35 (1H, m) 2.48 (1H, dd, J = 8.0, 4.0 Hz) 2.68-2.89 (2H, m) 3.12-3.22 (2H, m) 4.01-4.08 (2H, m) 4.18 (1H, t, J = 4.0 Hz) 4.75 (3H, s) 6.42 (1H, d, J = 8.0 Hz) 6.75 (1H, dd, J = 8.0, 4.0 Hz) 7.00-7.09 (6H, m) 7.12-7.16 (2H, m) 7.66 (1H, d, J = 4.0 Hz) 401 CD₃OD 400 0.94 (3H, d, J = 6.6 Hz) 0.99 (3H, d, J = 6.6 Hz) 1.17 (3H, d, J = 6.9 Hz) 2.16 (3H, s) 2.68-2.76 (1H, m) 2.78-2.90 (1H, m) 3.04-3.18 (1H, m) 3.36-3.43 (1H, m) 4.00-4.18 (2H, m) 4.56-4.61 (1H, m) 4.83 (4H, br s) 6.48 (1H, d, J = 8.0 Hz) 7.04 (1H, dd, J = 8.0, 4.0 Hz) 7.26 (1H, dd, J = 8.0, 4.0 Hz) 7.30-7.35 (2h, m) 7.73 (1H, d, J = 4.0 Hz) 402 CD₃OD 400 1.33 (3H, d, J = 4.0 Hz) 1.37-1.44 (1H, m) 1.72-1.83 (6H, br m) 2.82-2.97 (3H, m) 3.00-3.07 (1H, m) 3.23-3.28 (1H, m) 3.47 (1H, br d, J = 4.0 Hz) 3.78-3.83 (1H, m) 4.07-4.19 (2H, m) 4.50-4.57 (1H, m) 4.81 (3H, br s) 6.87-6.94 (1H, m) 7.12 (1H, dd, J = 8.0, 4.0 Hz) 7.32-7.38 (2H, m) 7.61-7.67 (2H, m) 403 CD₃OD 400 1.05 (1H, t, J = 8.0 Hz) 1.39 (4H, d, J = 4.0 Hz) 1.45-1.53 (1H, m) 1.69-1.77 (4H, m) 2.57-2.68 (2H, m) 2.76 (2H, s) 2.79-2.87 (2H, m) 2.97-3.07 (1H, m) 3.11-3.23 (2H, m) 3.67-3.78 (1H, m) 4.04-4.18 (2H, m) 4.59-4.65 (1H, m) 6.86 (1H, d, J = 12.0 Hz) 7.07-7.77 (1H, m) 7.29-7.33 (2H, m) 7.62-7.66 (2H, m) 404 CD₃OD 400 1.47-1.57 (1H, br m) 1.85-2.04 (5H, br m) 2.82-3.10 (3H, m) 3.16-3.22 (1H, m) 3.36-3.37 (1H, m) 3.65 (1H, d, J = 4.0 Hz) 3.83-3.91 (2H, m) 4.20-4.32 (2H, m) 4.65-4.71 (1H, m) 4.99 (4H, br s) 7.01 (1H, dd, J = 8.0, 4.0 Hz) 7.22 (1H, dd, J = 8.0, 4.0 Hz) 7.44-7.48 (2H, m) 7.77-7.82 (2H, m) 405 CD₃OD 400 0.55-0.66 (1H, m) 0.74-0.94 (6H, m) 1.07-1.18 (1H, m) 1.87-1.97 (1H, m) 2.77 (6H, s) 2.81-2.91 (1H, m) 3.13 (1H, dd, J = 8.0, 4.0 Hz) 3.22-3.23 (1H, m) 3.56 (1H, d, J = 4.0 Hz) 4.13-4.34 (2H, m) 4.50-4.60 (1H, m) 4.81 (3H, s) 6.94 (1H, d, J = 4.0 Hz) 7.11-7.24 (4H, m) 7.66 (1H, s) 8.66-8.80 (1H, m) 406 CD₃OD 400 0.87-0.90 (7H, m) 2.34-2.41 (1H, m) 2.93 (7H, s) 3.00-3.03 (1H, m) 3.17-3.24 (1H, m) 3.69 (1H, d, J = 4.0 Hz) 4.22-4.31 (2H, m) 4.66-4.71 (1H, m) 4.98 (2H, br s) 7.02 (1H, d, J = 8.0 Hz) 7.21-7.39 (4H, m) 7.78 (1H, S) 7.83 (1H, dd, J = 8.0, 4.0 Hz) 407 CD₃OD 400 2.55-2.58 (1H, m) 2.74-2.80 (1H, m) 3.03 (6H, s) 3.08-3.14 (1H, m) 3.31-3.46 (1H, m) 4.07-4.11 (1H, m) 4.21-4.29 (2H, m) 4.33 (1H, t, J = 8.0 Hz) 4.93 (4H, br s) 6.91-7.00 (2H, m) 7.06 (1H, s) 7.15-7.25 (4H, m) 7.27-7.34 (3H, m) 7.70-7.73 (2H, m) 408 CD₃OD 400 1.12 (3H, t, J = 7.0 Hz), 1.40 (3H, d, J = 6.9 Hz), 2.63 (3H, s), 2.80-3.05 (5H, m), 3.73-3.78 (1H, m), 4.00-4.20 (2H, m), 4.58-4.62 (1H, m), 6.84 (1H, d, J = 9.1 Hz), 7.08-7.18 (4H, m), 7.59 (1H, s), 7.62 (1H, dd, J = 9.2, 2.0 Hz), 8.60 (1H, t, J = 5.7 Hz). 409 CD₃OD 400 0.97 (2H, d, J = 3.1 Hz), 1.11 (3H, d, J = 6.6 Hz), 1.20-1.22 (1H, m), 1.38 (3H, d, J = 6.6 Hz), 2.52 (3H, s), 2.73-2.84 (2H, m), 3.04-3.08 (1H, m), 3.78-3.83 (1H, m), 4.08-4.21 (2H, m), 6.86 (1H, d, J = 9.2 Hz), 7.09-7.19 (4H, m), 7.60 (1H, s), 7.62 (1H, d, J = 8.9 Hz), 8.64 (1H, t, J = 5.7 Hz). 410 CD₃OD 400 1.11-1.18 (6H, m), 1.39 (3H, d, J = 7.0 Hz), 2.66-2.71 (1H, m), 2.80-3.05 (5H, m), 3.77-3.83 (1H, m), 4.04-4.20 (2H, m), 4.59-4.63 (1H, m), 6.85 (1H, d, J = 9.6 Hz), 7.08-7.19 (4H, m), 7.59 (1H, d, J = 1.0 Hz), 7.63 (1H, dd, J = 9.2, 2.1 Hz), 8.61 (1H, t, J = 5.7 Hz). 411 CD₃OD 400 1.32-1.38 (1H, m) 1.43 (2H, d, J = 8.0 Hz) 1.55 (3H, d, J = 8.0 Hz) 1.79-1.84 (3H, m) 1.93-2.00 (2H, m) 2.78-2.87 (1H, m) 2.93-3.04 (2H, m) 3.12-3.27 (2H, m) 3.54-3.64 (1H, m) 3.85-3.94 (1H, m) 4.22-4.34 (2H, m) 4.65-4.69 (1H, m) 4.77-4.82 (1H, m) 7.01 (1H, dd, J = 8.0, 4.0 Hz) 7.21-7.39 (5H, m) 7.76 (1H, d, J = 4.0 Hz) 7.79-7.87 (1H, m) 412 CD₃OD 400 1.40-1.67 (1H, br m) 1.88-1.91 (5H, m) 2.93-3.01 (3H, m) 3.19-3.26 (1H, m) 3.34-3.37 (1H, m) 3.42-3.44 (1H, m) 3.52 (1H, d, J = 12.0 Hz) 3.86-3.99 (2H, m) 4.26 (2H, q, J = 8.0 Hz) 4.74 (1H, dd, J = 8.0, 4.0 Hz) 5.01 (3H, br s) 6.98 (1H, d, J = 8.0 Hz) 7.22-7.33 (4H, m) 7.67 (1H, s) 7.78 (1H, dd, J = 8.0, 4.0 Hz) 413 CD₃OD 400 1.25 (3H, s), 1.56 (3H, d, J = 7.0 Hz), 2.35 (3H, s), 2.76 (5H, s), 2.92-2.97 (1H, m), 3.14-3.19 (1H, m), 3.88-3.93 (1H, m), 4.21-4.35 (2H, m), 4.75-4.79 (1H, m), 6.99 (1H, d, J = 9.3 Hz), 7.08-7.13 (3H, m), 7.19-7.23 (1H, m), 7.72 (1H, s), 7.62 (1H, dd, J = 9.2, 1.9 Hz), 8.74 (1H, t, J = 5.7 Hz). 414 CD₃OD 400 0.91 (2H, s), 1.07 (3H, d, J = 6.4 Hz), 1.20-1.22 (1H, m), 1.37 (3H, d, J = 6.5 Hz), 2.19 (3H, s), 2.50 (3H, s), 2.62 (1H, s), 2.72-2.78 (1H, m), 3.00-3.05 (1H, m), 3.75-3.80 (1H, m), 4.07-4.20 (2H, m), 6.84 (1H, d, J = 9.2 Hz), 6.92-6.98 (3H, m), 7.03-7.07 (1H, m), 7.58 (1H, s), 7.63 (1H, d, J = 8.7 Hz), 8.61 (1H, t, J = 5.7 Hz). 415 CD₃OD 400 1.05-1.09 (6H, m), 1.38 (3H, d, J = 6.8 Hz), 2.18 (3H, s), 2.58-2.67 (1H, m), 2.74-3.02 (5H, m), 3.77 (1H, q, J = 6.9 Hz), 4.04-4.20 (2H, m), 4.61-4.65 (1H, m), 6.83 (1H, d, J = 9.2 Hz), 6.91-6.97 (3H, m), 7.01-7.06 (1H, m), 7.56 (1H, s), 7.59 (1H, dd, J = 9.1, 2.1 Hz), 8.58 (1H, t, J = 5.8 Hz). 416 CD₃OD 400 1.08 (3H, br s), 1.40 (3H, d, J = 7.0 Hz), 2.63 (6H, br s), 2.91-2.96 (1H, m), 3.11-3.16 (1H, m), 3.76 (1H, q, J = 6.6 Hz), 4.12 (2H, s), 4.62-4.66 (1H, m), 6.84 (1H, d, J = 9.1 Hz), 7.36-7.48 (4H, m), 7.59 (1H, d, J = 1.1 Hz), 7.64 (1H, dd, J = 9.2, 2.1 Hz), 8.64 (1H, t, J = 5.7 Hz). 417 CD₃OD 400 1.08 (3H, br s), 1.25 (3H, d, J = 6.6 Hz), 1.35-1.42 (1H, m), 1.55 (3H, d, J = 6.8 Hz), 2.67 (3H, s), 2.88 (1H, s), 3.05-3.11 (1H, m), 3.30-3.35 (1H, m), 3.96 (1H, q, J = 6.8 Hz), 4.31 (2H, s), 7.02 (1H, d, J = 9.2 Hz), 7.53-7.67 (4H, m), 7.78 (1H, s), 7.84 (1H, d, J = 9.1 Hz), 8.83 (1H, t, J = 5.6 Hz). 418 CD₃OD 400 1.22-1.30 (6H, m), 1.56 (3H, d, J = 6.9 Hz), 2.78-2.83 (1H, m), 3.06-3.33 (5H, m), 3.95 (1H, q, J = 6.9 Hz), 4.25-4.34 (2H, m), 4.81-4.85 (1H, m), 7.01 (1H, d, J = 9.5 Hz), 7.53-7.65 (4H, m), 7.77 (1H, d, J = 1.4 Hz), 7.81 (1H, dd, J = 9.2, 2.1 Hz), 8.81 (1H, t, J = 5.6 Hz),. 419 CD₃OD 400 1.37-1.40 (2H, m) 1.55 (2H, d, J = 8.0 Hz) 1.62-1.94 (5H, m) 2.70-2.85 (1H, m) 2.91-2.99 (2H, m) 3.03-3.20 (2H, m) 3.28-3.42 (2H, m) 3.50-3.59 (1H, m) 3.83-3.88 (1H, m) 3.92-3.99 (1H, m) 4.20-4.33 (2H, m) 4.71-4.78 (1H, m) 4.84-4.89 (1H, m) 7.01 (1H, d, J = 8.0 Hz) 7.51-7.72 (4H, m) 7.77 (1H, s) 7.83 (1H, dd, J = 8.0, 4.0 Hz) 420 CD₃OD 400 1.55 (1H, br s) 1.87 (5H, br s) 2.93-3.11 (3H, m) 3.28-3.37 (2H, m) 3.50 (1H, br s) 3.85-3.99 (2H, m) 4.24-4.32 (2H, m) 4.75-4.81 (1H, m) 5.00 (5H, br, s) 7.00 (1H, d, J = 8.0 Hz) 7.50-7.62 (3H, m) 7.75-7.86 (2H, m) 421 CD₃OD 400 1.41 (2H, d, J = 8.0 Hz) 1.56 (1H, br t, J = 4.0 Hz) 1.88 (5H, br s) 2.92-3.13 (3H, m) 3.25-3.30 (1H, m) 3.36-3.57 (3H, m) 3.83-3.97 (1H, m) 4.22-4.41 (2H, m) 4.71-4.78 (1H, m) 4.91-4.96 (4H, m) 6.99-7.04 (1H, m) 7.49 (2H, d, J = 8.0 Hz) 7.63 (2H, d, J = 8.0 Hz) 7.79-7.82 (2H, m) 422 CD₃OD 400 1.32-1.42 (1H, m) 1.56 (3H, d, J = 8.0 Hz) 1.72-1.92 (5H, m) 2.86-2.97 (3H, m) 3.04-3.14 (1H, m) 3.25-3.46 (2H, m) 3.56 (1H, br s) 3.79-3.84 (1H, m) 4.22-4.35 (2H, m) 4.82-4.96 (4H, m) 6.99-7.06 (1H, m) 7.48-7.55 (2H, m) 7.64 (2H, d, J = 8.0 Hz) 7.79-7.84 (2H, m) 423 CD₃OD 400 1.36-1.57 (1H, m) 1.87 (5H, br s) 2.93-3.09 (3H, m) 3.20-3.37 (2H, m) 3.39 (1H, br s) 3.82-3.98 (2H, m) 4.27-4.31 (2H, m) 4.74-4.78 (1H, m) 4.94 (4H, br s) 7.00 (1H, d, J = 8.0 Hz) 7.50-7.57 (2H, m) 7.61-7.68 (2H, m) 7.78-7.83 (2H, m) 424 CD₃OD 400 0.71-0.81 (1H, m) 0.85-0.93 (6H, m) 1.21-1.44 (1H, m) 2.04-2.11 (1H, m) 2.98 (6H, s) 3.01-3.08 (1H, m) 3.19-3.27 (1H, m) 3.78 (1H, d, J = 4.0 Hz) 4.31-4.39 (2H, m) 4.65-4.69 (1H, m) 5.00 (3H, br s) 6.84-6.89 (1H, m) 6.99 (2H, d, J = 4.0 Hz) 7.05 (1H, d, J = 12.0 Hz) 73.82 (1H, s) 7.88 (1H, dd, J = 8.0, 4.0 Hz) 9.01 (1H, d, J = 4.0 Hz) 425 CD₃OD 400 1.45 (2H, d, J = 8.0 Hz) 1.57 (2H, d, J = 8.0 Hz) 1.86 (3H, br s) 1.95 (1H, d, J = 8.0 Hz) 2.84-2.93 (1H, m) 3.00-3.06 (1H, m) 3.14-3.27 (1H, m) 3.35-3.37 (1H, m) 3.60 (1H, br s) 3.87-3.96 (1H, m) 4.23-4.35 (2H, m) 4.61-4.71 (1H, m) 4.73-4.81 (1H, m) 4.97 (5H, s) 6.84-6.97 (3H, m) 6.98-7.08 (1H, m) 7.78-7.81 (1H, m) 7.85-7.94 (1H, m) 426 CD₃OD 400 1.05 (2H, d, J = 8.0 Hz) 1.24 (3H, d, J = 8.0 Hz) 1.32 (1H, d, J = 4.0 Hz) 1.49-1.72 (6H, br m) 2.95-3.01 (1H, m) 3.15-3.21 (1H, m) 3.26 (1H, d, J = 6.4 Hz) 3.36-3.37 (2H, m) 3.75-3.87 (2H, m) 4.14-4.28 (2H, m) 4.71-4.77 (1H, m) 4.98 (2H, s) 7.01 (1H, d, J = 8.0 Hz) 7.21-7.31 (4H, m) 7.75-7.83 (2H, m) 8.79-8.89 (1H, m) 427 CD₃OD 400 1.01 (6H, dd, J = 6.24, 14.0 Hz), 1.34 (3H, s, br), 1.43 (3H, s, br), 1.60 (3H, d, J = J = 6.83 Hz), 1.64-1.75 (4H, m), 2.79 (3H, s), 3.57 (1H, s, br), 4.10 = 4.12 (1H, m), 4.26-4.46 (3H, m), 4.91 (2H, s), 7.04 (1H, d, J = 8.17 Hz) 7.80 (1H, d, J = 1.4 Hz), 7.92 (1H, dd, J = 2.2, 9.28 Hz), 8.79-8.82 (1H, m) 428 CD₃OD 400 1.19-1.21 (6H, br m) 2.50 (3H, s) 2.95-3.05 (1H, m) 3.11-3.27 (5H, m) 3.33-3.36 (1H, m) 3.89-4.09 (2H, m) 4.19-4.30 (2H, m) 4.68 (1H, t, J = 4.0 Hz) 4.94 (2H, br s) 6.82 (1H, d, J = 8.0 Hz) 7.00-7.05 (2H, m) 7.25-7.33 (2H, m) 7.72 (1H, d, J = 8.0 Hz) 8.70 (1H, t, J = 4.0 Hz) 429 CD₃OD 400 0.99 (2H, d, J = 4.0 Hz) 1.24 (3H, d, J = 4.0 Hz) 1.33 (1H, d, J = 4.0 Hz) 1.47-1.59 (2H, m) 1.62-1.74 (2H, m) 1.78-1.93 (3H, m) 2.52 (3H, s) 2.92-3.01 (1H, m) 3.15-3.19 (1H, m) 3.53 (2H, t, J = 4.0 Hz) 3.79-3.92 (2H, m) 4.02-4.22 (1H, m) 4.26-4.32 (2H, m) 4.71 (1H, t, J = 8.0 Hz) 6.83 (1H, d, J = 8.0 Hz) 7.03-7.09 (1H, m) 7.12-7.27 (2H, m) 7.76 (2H, d, J = 8.0 Hz) 8.76 (1H, t, J = 4.0 Hz) 430 CD₃OD 400 1.58 (1H, br s) 1.88-1.91 (6H, br m) 2.51 (3H, s) 2.91-3.03 (3H, m) 3.10-3.13 (1H, m) 3.37-3.42 (1H, m) 3.51-3.53 (1H, br d, J = 8.0 Hz) 3.89-3.99 (2H, m) 4.17-4.31 (2H, m) 4.66 (1H, dd, J = 8.0, 4.0 Hz) 4.96 (2H, br s) 6.82 (1H, d, J = 8.0 Hz) 7.01-7.08 (2H, m) 7.14-7.24 (2H, m) 7.75 (1H, d, J = 12.0 Hz) 434 CD₃OD 400 1.02-1.47 (12H, m), 1.58-1.77 (17H, m), 2.94 (6H, s), 4.06 (1H, q, J = 6.89 Hz), 4.22-4.27 (1H, m), 4.34-4.40 (1H, m), 4.65 (1H, d, J = 7.6 Hz), 7.04 (1H, d, J = 9.1 Hz), 7.85 (1H, d, J = 1.5 Hz), 7.97 (1H, dd, J = 2.1, 9.2 Hz), 8.77-8.80 (1H, m). 435 CD₃OD 400 1.07-1.51 (17H, m), 1.64 (3H, d, J = 6.89 Hz), 1.73-1.84 (3H, m), 2.08 (1H, d, J = 11.08 Hz), 2.79 (3H, s), 3.73-3.77 (2H, m), 4.22-4.27 (1H, m), 4.33-4.41 (2H, m), 4.60 (1H, d, J = 3 Hz), 7.04 (1H, d, J = 9.25 Hz), 7.82 (1H, d, J = 1.68 Hz), 7.95 (1H, dd, J = 6.0, 2.08 Hz), 8.71-8.79 (1H, m). 436 CD₃OD 400 0.98-1.19 (3H, m), 1.24-1.44 (14H, m), 1.62 (3H, d, J = 6.8 Hz), 1.73-1.92 (3H, m), 2.10 (1H, d, J = 13.21 Hz), 2.78 (3H, s), 3.76 (2H, dd, J = 3.04 Hz, 8.24 Hz), 4.26-4.33 (1H, m), 4.37 (2H, d, J = 2.6 Hz), 4.60 (1H, d, J = 3 Hz), 7.04 (1H, d, J = 9.05 Hz), 7.82 (1H, d, J = 1.12 Hz), 7.95 (1H, dd, J = 9.17, 2.08 Hz), 8.71-8.79 (1H, m). 437 CD₃OD 400 0.97-1.51 (14H, m), 1.58 (3H, d, J = 6.65 Hz), 1.73-1.95 (8H, m), 2.79 (3H, s), 3.13 (3H, s), 4.26-4.37 (2H, m), 4.59-4.73 (1H, m), 5.17-5.21 (1H, m), 7.04 (1H, d, J = 7.36 Hz) 7.79 (1H, d, J = 1.1 Hz), 7.92 (1H, d, J = 7.84 Hz), 7.93 (1H, dd, J = 9.2, 2.08 Hz) 8.58-8.87 (1H, m) 438 CD₃OD 400 0.97-1.33 (7H, m), 1.38 (6H, t, J = 7.2 Hz), 1.58 (3H, d, J = 6.81 Hz), 1.72-1.96 (8H, m), 3.12 (3H, s), 4.25-4.36 (2H, m), 4.51 (1H, dd, J = 7.0, 13.49 Hz), 4.91 (4H, s), 5.20-5.24 (1H, m), 7.04 (1H, d, J = 9.13 Hz) 7.791 (1H, d, J = 1.2 Hz), 7.92 (1H, dd, J = 2.12, 9.21 Hz), 8.58-8.78 (1H, m) 439 CD₃OD 400 0.99-1.00 (2H, m), 1.07 (6H, t, J = 7.24 Hz), 1.22-1.40 (6H, m), 1.61 (3H, d, J = 6.92 Hz), 1.66-1.87 (10H, m), 3.10-3.19 (2H, m, br), 3.21-3.28 (2H, m), 4.13 (1H, dd, J = 7.37, 13.84 Hz), 4.32 (2H, d, J = 5.72 Hz), 4.49 (1H, dd, J = 6.08, 9.2 Hz), 4.91 (2H, s), 7.04 (1H, d, J = 9.25 Hz) 7.81 (1H, s), 7.93 (1H, dd, J = 2.04, 9.16 Hz), 8.77-8.80 (1H, m)

TABLE 15 Names of the examples. Example No. Name 12 (S)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide 13 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)carbamoyl]-2- (decahydro-naphthalen-1-yl)-ethyl]-3-(4-chloro-phenyl)-propionamide 14 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2- (decahydro-naphthalen-1-yl)-ethyl]-3-methyl-butyramide 15 (R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide 16 (R)-2-Amino-4-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide 17 (S)-2-(2-Amino-acetylamino)-N-(6-amino-pyridin-3-ylmethyl)-3- (decahydro-naphthalen-1-yl)-propionamide 18 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2- (decahydro-naphthalen-1-yl)-ethyl]-propionamide 19 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(decahydro-naphthalen-1-yl)-2- (2-methylamino-acetylamino)-propionamide 20 (R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide 21 (R)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide 22 (R)-2-Amino-N-{(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2- naphthalen-1-yl-ethyl}-3-methyl-butyramide 23 (R)-Pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 24 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide 25 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide 26 (R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-phenyl-ethyl}-amide 27 (R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide 28 (R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-o-tolyl-ethyl}-amide 29 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide 30 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 31 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-cyano-phenyl)-ethyl]-amide 32 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 33 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 34 (R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-2-yl-ethyl}-amide 35 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 36 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide 37 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-amide 38 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide 39 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide 40 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide 41 (R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide 42 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 43 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 44 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 45 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 46 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide 47 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-amide 48 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide 49 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide 50 (R)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-pentafluorophenyl-ethyl}-amide 51 (R)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide 52 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(4-tert-butyl-phenyl)-ethyl]-amide 53 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 54 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2- (3,4-dichloro-phenyl)-ethyl]-3-phenyl-propionamide 55 (R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 56 (S)-Thiazolidine-4-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 57 (S)-2-((R)-2-Amino-2-phenyl-acetylamino)-N-(6-amino-pyridin-3- ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide 58 (S)-2-((S)-2-Amino-2-phenyl-acetylamino)-N-(6-amino-pyridin-3- ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide 59 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2- (3,4-dichloro-phenyl)-ethyl]-3-(4-chloro-phenyl)-propionamide 60 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-2-methylamino-3-phenyl-propionamide 61 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2- (3,4-dichloro-phenyl)-ethyl]-3,3-dimethyl-butyramide 62 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-2-methylamino-propionamide 63 (R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 64 (R)-1,2,3,4-Tetrahydro-isoquinoline-3-carboxylic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 65 (R)-2,5-Dihydro-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 66 (R)-4,4-Difluoro-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 67 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2- (3,4-dichloro-phenyl)-ethyl]-4-phenyl-butyramide 68 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2- (3,4-dichloro-phenyl)-ethyl]-3-cyclohexyl-propionamide 69 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-(2- methylamino-acetylamino)-propionamide 70 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3- trifluoromethyl-phenyl)-ethyl]-3-(4-chloro-phenyl)-propionamide 71 (R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 72 (R)-Pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 73 (R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 74 (R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 75 (R)-Piperidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-naphthalen-1-ylethyl}- amide 76 (R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide 77 (R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 78 (R)-Piperidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide 79 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2- methylamino-acetylamino)-propionamide 80 (R)-2-Amino-N-[(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2- (3,4-difluoro-phenyl)-ethyl]-3-phenyl-propionamide 81 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)carbamoyl]-2-(3,4-difluoro- phenyl)-ethyl]-2-methylamino-3-phenyl-propionamide 82 (S)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 83 (S)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 84 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-methylamino-propionamide 85 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-methylamino-propionamide 86 N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro- phenyl)-ethyl]-2-methyl-2-methylamino-propionamide 87 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-methylamino-propionamide 88 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-methylamino-propionamide 89 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-3-methyl-2-methylamino-butyramide 90 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 91 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 92 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 93 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide 94 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide 95 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide 96 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide 97 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-pentafluorophenyl-ethyl}-amide 98 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 99 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide 100 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-methoxy-phenyl)-ethyl]-amide 101 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-phenyl-ethyl}-amide 102 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-tert-butyl-phenyl)-ethyl]-amide 103 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 104 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-o-tolyl-ethyl}-amide 105 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide 106 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-p-tolyl-ethyl}-amide 107 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-methoxy-phenyl)-ethyl]-amide 108 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-fluoro-phenyl)-ethyl]-amide 109 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide 110 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2,4-dichloro-phenyl)-ethyl]-amide 111 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide 112 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-pyridin-4-yl-ethyl}-amide 113 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide 114 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-quinolin-2-yl-ethyl}-amide 115 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide 116 (S)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 117 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 118 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 119 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 120 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 121 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-o-tolyl-ethyl}-amide 122 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide 123 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-p-tolyl-ethyl}-amide 124 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3-methoxy-phenyl)-ethyl]-amide 125 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(2-fluoro-phenyl)-ethyl]-amide 126 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide 127 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(2,4-dichloro-phenyl)-ethyl]-amide 128 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide 129 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-pyridin-4-yl-ethyl}-amide 130 (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide 131 (R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 132 (R)-1-Propyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 133 (R)-1-Isobutyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 134 {(R)-2-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethylcarbamoyl]-pyrrolidin-1-yl}-acetic acid methyl ester 135 {(R)-2-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethylcarbamoyl]-pyrrolidin-1-yl}-acetic acid 136 (R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 137 (R)-1-Ethyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide 138 (R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 139 (R)-1-Propyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 140 (R)-1-Benzyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 141 (R)-1-Benzyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 142 (R)-1-(4-Chloro-benzyl)-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 143 (R)-1-(3-Chloro-benzyl)-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 144 (R)-1-Methyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 145 (R)-1-Methyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 146 (R)-1-Isopropyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 147 (R)-1-Isopropyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 148 (2R,4R)-4-Hydroxy-1-methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6- amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]- amide 149 (R)-2-Methyl-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [(S)-1- [(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)- ethyl]-amide 150 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-[2- (isopropyl-methyl-amino)-acetylamino]-propionamide 151 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide 152 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-[2-(benzyl-methyl-amino)- acetylamino]-3-(3,4-dichloro-phenyl)-propionamide 153 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-(2- dimethylamino-acetylamino)-propionamide 154 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-[2- (isobutyl-methyl-amino)-acetylamino]-propionamide 155 (R)-2-(Isopropyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6- amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]- amide 156 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2- (isopropyl-methyl-amino)-acetylamino]-propionamide 157 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2- diisopropylamino-acetylamino)-propionamide 158 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2- dipropylamino-acetylamino)-propionamide 159 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2- diisobutylamino-acetylamino)-propionamide 160 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2- phenethylamino-acetylamino)-propionamide 161 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2- (methyl-phenethyl-amino)-acetylamino]-propionamide 162 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-{2- [methyl-((E)-3-phenyl-allyl)-amino]-acetylamino}-propionamide 163 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-{2-[(4-chloro-benzyl)-methyl- amino]-acetylamino}-3-(3,4-difluoro-phenyl)-propionamide 164 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-{2-[(3-chloro-benzyl)-methyl- amino]-acetylamino}-3-(3,4-difluoro-phenyl)-propionamide 165 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-{2-[(2-chloro-benzyl)-methyl- amino]-acetylamino}-3-(3,4-difluoro-phenyl)-propionamide 166 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-{2-[(4- methoxy-benzyl)-methyl-amino]-acetylamino}-propionamide 167 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-[2-(butyl-methyl-amino)- acetylamino]-3-(3,4-difluoro-phenyl)-propionamide 168 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2- (isobutyl-methyl-amino)-acetylamino]-propionamide 169 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-[2-(cyclohexylmethyl-methyl- amino)-acetylamino]-3-(3,4-difluoro-phenyl)-propionamide 170 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2- piperidin-1-yl-acetylamino)-propionamide 171 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2- morpholin-4-yl-acetylamino)-propionamide 172 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-3,4- dihydro-1H-isoquinolin-2-yl-acetylamino)-propionamide 173 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-3,4- dihydro-2H-quinolin-1-yl-acetylamino)-propionamide 174 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-[2- (methyl-phenyl-amino)-acetylamino]-propionamide 175 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide 176 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide 177 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(isobutyl-methyl-amino)-propionamide 178 (R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 179 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-dimethylamino-3,3-dimethyl-butyramide 180 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide 181 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide 182 (R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 183 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-dimethylamino-3,3-dimethyl-butyramide 184 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-isopropylamino-3-phenyl-propionamide 185 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-dimethylamino-3-phenyl-propionamide 186 (R)-2-Amino-N-[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)- carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-3-methyl-butyramide 187 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]- amide 188 (2R)-3-Methyl-2-methylamino-pentanoic acid [(R)-1-[(6-amino-2- methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]- amide 189 (R)-Pyrrolidine-2-carboxylic acid [(R)-1-[(6-amino-2-methyl-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 190 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(R)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 191 (S)-Thiazolidine-4-carboxylic acid [(R)-1-[(6-amino-2-methyl-pyridin- 3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 192 (R)-4,4-Difluoro-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2- methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]- amide 193 (S)—N-[(R)-1-[(6-Amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2- (3,4-dichloro-phenyl)-ethyl]-2-methylamino-3-phenyl-propionamide 194 (R)-2-Amino-N-[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-(4-fluoro-phenyl)- propionamide 195 (R)-2-Amino-N-[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-(4-chloro-phenyl)- propionamide 196 (R)-2-Amino-N-[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-pyridin-3-yl-propionamide 197 (R)—N-(6-Amino-2-methyl-pyridin-3-ylmethyl)-2-((S)-2-amino-2- phenyl-acetylamino)-3-(3,4-dichloro-phenyl)-propionamide 198 (S)-2-((R)-2-Amino-2-cyclohexyl-acetylamino)-N-(6-amino-2-methyl- pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-propionamide 199 (R)-2-Amino-N-[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3,3-dimethyl-butyramide 200 (R)-2-Amino-N-[(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-3-cyclohexyl-propionamide 201 (R)-Piperidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 202 (R)-1,2,3,4-Tetrahydro-quinoline-2-carboxylic acid [(S)-1-[(6-amino-2- methyl-pyridin-3-ylmethyl)-carbamoyl]- 2-(3,4-dichloro-phenyl)-ethyl]-amide 203 (R)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-2- methyl-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 204 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 205 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 206 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2,4- dimethyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)- ethyl]-amide 207 (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-2,4- dimethyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)- ethyl]-amide 208 (R)-2-Amino-3-methyl-pentanoic acid [(S)-1-[(6-amino-2,4-dimethyl- pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]- amide 209 (R)-2-Amino-3-methyl-pentanoic acid {(S)-1-[(6-amino-5-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 210 (R)-1-Methanesulfonyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 211 (R)-2-Methanesulfonylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 212 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-2-(methanesulfonyl-methyl-amino)- propionamide 213 (R)-2-(Methanesulfonyl-methyl-amino)-3-methyl-pentanoic acid {(S)-1- [(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl- ethyl}-amide 214 (R)-2-Amino-3-methyl-pentanoic acid {(R)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide 215 (S)-Pyrrolidine-2-carboxylic acid {(R)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2,2-dicyclohexyl-ethyl}-amide 216 (S)-2-Amino-N-{(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2- dicyclohexyl-ethyl}-3-phenyl-propionamide 217 (S)-2-Amino-N-{(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2- dicyclohexyl-ethyl}-3,3-dimethyl-butyramide 218 (S)—N-{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2- dicyclohexyl-ethyl}-2-methylamino-propionamide 219 (S)-3-Methyl-2-methylamino-pentanoic acid {(R)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide 220 (R)-2-(2-Amino-acetylamino)-N-(6-amino-pyridin-3-ylmethyl)-3,3- dicyclohexyl-propionamide 221 (R)—N-(6-Amino-pyridin-3-ylmethyl)-3,3-dicyclohexyl-2-(2- methylamino-acetylamino)-propionamide 222 (R)—N-(6-Amino-pyridin-3-ylmethyl)-3,3-dicyclohexyl-2-(2- dimethylamino-acetylamino)-propionamide 223 (S)-1-Methyl-pyrrolidine-2-carboxylic acid {(R)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide 224 (S)-2-Amino-3-methyl-pentanoic acid {(1R,2R)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-hydroxy-2-phenyl-ethyl}-amide 225 (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-phenyl-ethyl}-methyl-amide 227 1H-Pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide 228 1H-Pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 229 1H-Pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 230 3,4,5-Trimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 231 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 232 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 233 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 234 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide 235 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 236 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide 237 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-phenyl-ethyl}-amide 238 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide 239 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide 240 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide 241 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide 242 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 243 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 244 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-o-tolyl-ethyl}-amide 245 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide 246 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide 247 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-amide 248 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide 249 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide 250 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide 251 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-pentafluorophenyl-ethyl}-amide 252 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-biphenyl-4-yl-ethyl}-amide 253 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-p-tolyl-ethyl}-amide 254 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-methoxy-phenyl)-ethyl]-amide 255 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-ethoxy-phenyl)-ethyl]-amide 256 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-tert-butyl-phenyl)-ethyl]-amide 257 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-quinolin-2-yl-ethyl}-amide 258 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-trifluoromethyl-phenyl)-ethyl]-amide 259 4-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 260 4-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 261 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 262 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide 263 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2,5-dichloro-phenyl)-ethyl]-amide 264 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 265 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-fluoro-phenyl)-ethyl]-amide 266 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 267 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-chloro-phenyl)-ethyl]-amide 268 3-Methyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide 269 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide 270 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide 271 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 272 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-trifluoromethyl-phenyl)-ethyl]-amide 273 3-Methyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide 274 5-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3- trifluoromethyl-phenyl)-ethylcarbamoyl]-1H-pyrrole-2-carboxylic acid methyl ester 275 5-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3- trifluoromethyl-phenyl)-ethylcarbamoyl]-1H-pyrrole-2-carboxylic acid 276 5-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3- trifluoromethyl-phenyl)-ethylcarbamoyl]-4-methyl-1H-pyrrole-2- carboxylic acid 277 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]- amide 278 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 279 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 280 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 281 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide 282 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]- amide 283 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide 284 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 285 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 286 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 287 1H-Imidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 288 1H-Imidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide 289 1H-Imidazole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 290 1-Methyl-1H-imidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 291 2,5-Dimethyl-2H-pyrazole-3-carboxylic acid [(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 292 5-p-Tolyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 293 5-p-Tolyl-1H-pyrrole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide 294 5-p-Tolyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 295 5-p-Tolyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(2-chloro-phenyl)-ethyl]-amide 296 5-p-Tolyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 297 5-p-Tolyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 298 1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 299 1H-Benzoimidazole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 300 5-Methoxy-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 301 5-Fluoro-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 302 5-Hydroxy-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 303 1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 304 5-Methoxy-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 305 5-Fluoro-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 306 1-Methyl-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide 307 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 308 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 309 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3- ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 310 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]- amide 311 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide 312 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide 313 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 314 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 315 1H-Indole-2-carboxylic acid [(R)-1-[(6-amino-2-methyl-pyridin-3- ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 316 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 317 1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-m-tolyl-ethyl}-amide 318 5-Methoxy-1H-indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide 319 1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-2-methyl-pyridin-3- ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-amide 320 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 321 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 322 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3- ylmethyl)-carbamoyl]-2-(2-trifluoromethyl-phenyl)-ethyl]-amide 323 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide 324 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide 325 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 326 5-Fluoro-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 327 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 328 1H-Benzoimidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 329 1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-pentafluorophenyl-ethyl}-amide 330 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 331 5-Fluoro-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 332 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 333 1H-Benzoimidazole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide 334 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-(4-methoxy-phenyl)-ethyl]-amide 335 1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-benzo[b]thiophen-3-yl-ethyl}-amide 336 1H-Indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3- ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide 337 5-Methoxy-1H-indole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl- pyridin-3-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-amide 338 1H-Indole-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)- carbamoyl]-2-cyclohexyl-ethyl}-amide 339 (S)-3-Methyl-2-methylamino-pentanoic acid {(S)-1-[(6-amino-pyridin- 3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide 340 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-3-methyl-2-methylamino-butyramide 341 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro- phenyl)-ethyl]-3-methyl-2-methylamino-butyramide 342 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro- phenyl)-ethyl]-2-methylamino-3-phenyl-propionamide 343 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(cyclohexylmethyl-methyl-amino)- propionamide 344 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-dimethylamino-propionamide 345 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide 346 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(methyl-propyl-amino)-propionamide 347 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(butyl-methyl-amino)-propionamide 348 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-3-methyl- butyramide 349 (S)-2-(Isopropyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6- amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]- amide 350 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-diisopropylamino-propionamide 351 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-dimethylamino-3-phenyl-propionamide 352 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-3-phenyl-propionamide 353 (S)-2-(Isopropyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6- amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]- amide 354 N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro- phenyl)-ethyl]-2-piperidin-1-yl-propionamide 355 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-diethylamino-propionamide 356 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-pyrrolidin-1-yl-propionamide 357 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-pyrrolidin-1-yl-propionamide 358 (R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide 359 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-dimethylamino-3-methyl-butyramide 360 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-3-hydroxy-2-(isopropyl-methyl-amino)- propionamide 361 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-3-hydroxy- propionamide 362 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-diethylamino-3-hydroxy-propionamide 363 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-2-diethylamino-3-hydroxy-propionamide 364 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- difluoro-phenyl)-ethyl]-3-diethylamino-succinamic acid methyl ester 365 (S)—N-(6-Amino-pyridin-3-ylmethyl)- 3-(3,4-difluoro-phenyl)-2-[2-(2,6-dimethyl-piperidin-1-yl)- acetylamino]-propionamide 366 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2- pyrrolidin-1-yl-acetylamino)-propionamide 367 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide 368 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-(methyl-propyl-amino)-propionamide 369 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-(butyl-methyl-amino)-propionamide 370 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-(isopropyl-methyl-amino)-3-methyl-butyramide 371 (S)-2-(Isopropyl-methyl-amino)-3-methyl-pentanoic acid [(S)-1-[(6- amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]- amide 372 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-diisopropylamino-propionamide 373 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-(isopropyl-methyl-amino)-3-phenyl-propionamide 374 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-piperidin-1-yl-propionamide 375 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-piperidin-1-yl-propionamide 376 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro- phenyl)-ethyl]-2-diethylamino-propionamide 377 (R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide 378 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-[2-(2,6-dimethyl-piperidin-1-yl)- acetylamino]-3-(4-fluoro-phenyl)-propionamide 379 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(4-fluoro-phenyl)-2-(2- piperidin-1-yl-acetylamino)-propionamide 380 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-(2-diethylamino-acetylamino)-3- (4-fluoro-phenyl)-propionamide 381 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-(isopropyl-methyl-amino)-propionamide 382 (S)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-amide 383 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-(methyl-propyl-amino)-propionamide 384 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-(ethyl-methyl-amino)-propionamide 385 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-dipropylaminopropionamide 386 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-dimethylamino-3-hydroxy-propionamide 387 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-(ethyl-methyl-amino)-3-hydroxy-propionamide 388 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-3-hydroxy-2-(isopropyl-methyl-amino)-propionamide 389 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-diethylamino-3-hydroxy-propionamide 390 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-diethylamino-propionamide 391 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-dimethylamino-propionamide 392 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-cyclohexyl-2-[2-(2,6-dimethyl- piperidin-1-yl)-acetylamino]-propionamide 393 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-cyclohexyl-2-(2- diisopropylamino-acetylamino)-propionamide 394 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(decahydro-naphthalen-1-yl)-2- (2-diisopropylamino-acetylamino)-propionamide 395 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro- naphthalen-1-yl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide 396 (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3- ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-amide 397 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro- naphthalen-1-yl)-ethyl]-2-dimethylamino-3-phenyl-propionamide 398 (R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide 399 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-2-dimethylamino-3-methyl-butyramide 400 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-2-dimethylamino-3-phenyl-propionamide 401 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide 402 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide 403 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4- dichloro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide 404 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-dichloro-phenyl)-2-(2- piperidin-1-yl-acetylamino)-propionamide 405 (R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide 406 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro- phenyl)-ethyl]-2-dimethylamino-3-methyl-butyramide 407 (R)—N-[(S)-1-[6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro- phenyl)-ethyl]-2-dimethylamino-3-phenyl-propionamide 408 (S)—N-[(S)-1-[6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro- phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide 409 (S)—N-[(S)-1-[6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro- phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide 410 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro- phenyl)-ethyl]-2-diethylamino-propionamide 411 N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro- phenyl)-ethyl]-2-piperidin-1-yl-propionamide 412 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3-chloro-phenyl)-2-(2- piperidin-1-yl-acetylamino)-propionamide 413 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl- ethyl}-2-(ethyl-methyl-amino)-propionamide 414 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl- ethyl}-2-(isopropyl-methyl-amino)-propionamide 415 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl- ethyl}-2-diethylamino-propionamide 416 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3- trifluoromethyl-phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide 417 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3- trifluoromethyl-phenyl)-ethyl]-2-(isopropyl-methyl-amino)- propionamide 418 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3- trifluoromethyl-phenyl)-ethyl]-2-diethylamino-propionamide 419 N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3- trifluoromethyl-phenyl)-ethyl]-2-piperidin-1-yl-propionamide 420 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-(2-piperidin-1-yl-acetylamino)- 3-(3-trifluoromethyl-phenyl)-propionamide 421 (R)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4- trifluoromethyl-phenyl)-ethyl]-2-piperidin-1-yl-propionamide 422 (S)—N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4- trifluoromethyl-phenyl)-ethyl]-2-piperidin-1-yl-propionamide 423 (S)—N-(6-Amino-pyridin-3-ylmethyl)-2-(2-piperidin-1-yl-acetylamino)- 3-(4-trifluoromethyl-phenyl)-propionamide 424 (R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino- pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide 425 N-[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro- phenyl)-ethyl]-2-piperidin-1-yl-propionamide 426 (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(4-chloro-phenyl)-2-[2-(2,6- dimethyl-piperidin-1-yl)-acetylamino]-propionamide 427 (S)-2-[(S)-2-(Isopropyl-methyl-amino)-propionylamino]-4-methyl- pentanoic acid (6-amino-pyridin-3-ylmethyl)-amide 428 (S)—N-(6-Amino-2-methyl-pyridin-3-ylmethyl)-2-(2-diethylamino- acetylamino)-3-(4-fluoro-phenyl)-propionamide 429 (S)—N-(6-Amino-2-methyl-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)- 2-[2-(2,6-dimethyl-piperidin-1-yl)-acetylamino]-propionamide 430 (S)—N-(6-Amino-2-methyl-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)- 2-(2-piperidin-1-yl-acetylamino)-propionamide 431 (R)—N-[(S)-1-[(6-Amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2- (3,4-difluoro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide 432 (S)—N-[(S)-1-[(6-Amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2- (3,4-difluoro-phenyl)-ethyl]-2-piperidin-1-yl-propionamide 433 (S)—N-{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2- dicyclohexyl-ethyl}-2-(isopropyl-methyl-amino)-propionamide 434 (S)—N-{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2,2- dicyclohexyl-ethyl}-2-dimethylamino-propionamide 435 (S)—N-{(R)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- 2-hydroxy-ethyl}-2-(isopropyl-methyl-amino)-propionamide 436 (R)—N-(6-Amino-pyridin-3-ylmethyl)-3-cyclohexyl-2-[(S)-2-(isopropyl- methyl-amino)-propionylamino]-butyramide 437 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-(isopropyl-methyl-amino)-N-methyl-propionamide 438 S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-diethylamino-N-methyl-propionamide 439 (S)—N-{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl- ethyl}-2-dipropylamino-propionamide

Biological Methods

The ability of the compounds of formula (I) to inhibit KLK1 may be determined using the following biological assays:

Determination of the IC₅₀ for KLK1

KLK1 inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Stürzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human KLK1 (Callbiochem) was incubated at 37° C. with the fluorogenic substrate H-DVal-Leu-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC₅₀ value for the test compound was determined.

Determination of Enzyme Selectivity

Selected compounds were further screened for inhibitory activity against other trypsin-like serine proteases using the appropriate enzyme and chromogenic substrate (Chromogenix AB). The activity against the following human enzymes was tested (substrate in brackets):—plasma kallikrein (S-2302), thrombin (S-2238), plasmin (S-2390) and trypsin (S-2222). The enzyme was incubated at 37° C. with the chromogenic substrate. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 405 nm.

Data acquired from these assays are shown in Tables 16 and 17 below:

TABLE 16 (In vitro activity) Example No IC₅₀ vs KLK1 (nM) 1 0.96 2 1.0 3 0.22 4 0.7 5 1.3 6 2.0 7 10.5 8 1.7 9 6.3 10 13.7 11 4.9 12 6.3 13 9.8 14 0.96 15 1.2 16 1.1 17 211 18 5.0 19 21.6 20 4.3 21 22.8 22 2.2 24 27.8 25 9.8 26 20.5 27 2.5 28 32.1 29 10.2 30 1.1 31 18.1 32 2.8 33 5.3 34 3.3 35 0.47 36 1.6 37 626 38 9.2 39 5.8 40 6.6 41 0.76 42 1.4 43 2.9 44 5.4 45 3.1 46 1.2 47 316 48 8.0 49 4.2 50 29.1 51 0.26 52 24.5 53 11.2 54 0.29 55 0.70 56 7.1 57 4.6 58 48.6 59 0.56 60 0.71 61 0.4 62 2.4 63 0.66 64 3.1 65 2.7 66 20.7 67 3.1 68 9.2 69 42.2 70 1.1 72 7.2 73 1.1 74 1.8 75 2.2 76 21.8 77 2.9 78 1.2 80 16.1 81 5.0 82 11.2 83 158 84 8.0 85 13.9 86 15.5 87 6.4 88 6.7 89 11.0 90 0.86 91 2.1 92 3.6 93 0.85 94 12.5 95 1.8 96 5.5 97 45.2 98 1.3 99 17.1 100 85.8 101 24.1 102 258 103 5.4 104 24.4 105 3.8 106 3.9 107 71.2 108 34.0 109 21.7 110 4.0 111 15.0 112 257 113 14.5 114 28.4 115 19.5 116 16.1 117 0.45 118 2.1 119 1.8 120 1.6 121 11.0 122 1.8 123 1.4 124 36.8 125 8.8 126 9.3 127 0.9 128 7.6 129 215 130 5.0 131 0.54 132 6.4 133 16.5 134 13.5 135 17.3 136 8.6 137 288 138 39.8 139 3.7 140 4.3 141 13.7 142 15.0 143 21.0 144 20.9 145 10.5 146 102 147 49.6 148 55.7 149 36.8 150 12.0 151 17.7 152 5.7 153 69.9 154 216 155 63.3 156 80.6 157 123.3 158 114.4 159 165.1 160 184.8 161 93.5 162 38.1 163 56.5 164 345 165 83.5 166 726 167 258 168 291 169 334 170 16.6 171 1.3 172 12.7 173 78.3 174 90.0 175 2.0 176 4.0 177 1.9 178 15.9 179 3.01 180 7.9 181 1.1 182 21.2 183 5.1 184 44.4 185 14.5 186 0.81 187 0.71 188 1.2 189 4.2 190 1.8 191 33.3 192 60.4 193 10.9 194 5.1 195 5.4 196 23.2 197 84.6 198 28.0 199 1.4 200 22.1 201 1.3 202 22.5 203 4.5 204 5.9 205 6.7 208 32.1 209 36.0 210 39.0 211 0.29 212 29.8 213 2.8 214 16.9 215 12.6 216 24.4 217 29.3 218 35.3 219 3.6 220 55.5 221 50.5 222 39.7 223 17.37 224 61.6 225 51.1 226 10.1 227 5.3 228 32.1 229 3.4 230 20.3 231 3.1 232 1.5 233 2.1 234 3.2 235 2.4 236 9.0 237 10.9 238 35.2 239 6.5 240 1.5 241 3.8 242 4.4 243 3.4 244 7.8 245 13.7 246 3.5 247 200 248 12.7 249 6.9 250 0.8 251 128 252 43.2 253 12.5 254 37.2 255 105 256 122 257 12.1 258 10.3 259 85.4 260 150 261 13.2 262 28.3 263 20.5 264 3.1 265 21.6 266 5.7 267 8.2 268 7.7 269 26.1 270 20.9 271 3.3 272 10.3 273 375 274 4.8 275 147 276 30.5 277 0.9 278 3.2 279 4.5 280 1.9 281 1.8 282 1.3 283 5.1 284 5.2 285 6.5 286 4.3 287 75.6 288 93.2 289 30.5 290 626 291 165 292 31.5 293 36.3 294 35.6 295 192 296 40.9 297 40.1 298 9.4 299 8.1 300 7.4 301 11.0 302 7.2 303 240 304 148 305 119 306 163 307 22.0 308 15.6 309 42.3 310 48.9 311 46.5 312 38.4 313 8.7 314 15.6 315 68.6 316 76.7 317 14.7 318 12.1 319 110 320 98.5 321 85.4 322 12.4 323 48.1 324 68.4 325 21.3 326 25.4 327 17.8 328 179 329 299 330 23.6 331 32.0 332 21.5 333 184 334 235 335 15.8 338 881 339 39.8 340 0.38 341 2.2 342 2.7 343 91.0 344 21.3 345 7.7 346 21.3 347 24.5 348 11.1 349 7.8 350 28.5 351 8.8 352 13.7 353 7.8 354 11.6 355 2.5 356 3.8 357 3.0 358 10.4 359 5.0 360 20.2 361 55.6 362 25.9 363 84.4 364 43.7 365 2.5 366 54.5 367 10.8 368 19.4 369 29.1 370 11.3 371 7.3 372 34.3 373 25.7 374 52.7 375 4.9 376 2.7 377 32.2 378 2.5 379 128 380 13.9 381 1.1 382 48.6 383 45.9 384 9.7 385 107 386 260 387 170 388 22.2 389 42.9 390 2.7 391 49.4 392 47.2 393 26.9 394 8.4 395 0.17 396 1.4 397 44.2 398 0.82 399 0.74 400 1.7 401 0.16 402 13.0 403 1.1 404 33.4 405 7.1 406 4.7 407 17.0 408 4.8 409 0.63 410 2.6 411 12.7 412 9.3 413 7.9 414 0.77 415 5.3 416 6.2 417 0.83 418 2.0 419 16.3 420 117 421 67.4 422 3.0 423 129 424 28.0 425 14.9 426 2.7 427 106 428 9.9 429 1.7 430 59.8 431 50.6 432 17.0 433 100 434 43.9 435 5.0 436 3.6 437 4.2 438 5.4 439 107

TABLE 17 (Selectivity data) IC₅₀ (nM) Example Plasma No Kallikrein Thrombin Trypsin Plasmin 1 >10000 >10000 >10000 >10000 2 >10000 >10000 >10000 >10000 3 >10000 >10000 >10000 >10000 4 >10000 >10000 >10000 >10000 5 >10000 >10000 >10000 >10000 11 >10000 >10000 >10000 >10000 13 >10000 >10000 >10000 >10000 20 >10000 >10000 >10000 >10000 25 >10000 >10000 >10000 >10000 26 >10000 >10000 >10000 >10000 27 >10000 >10000 >10000 >10000 29 >10000 >10000 >10000 >10000 30 >10000 >10000 >10000 >10000 54 >10000 >10000 >10000 >10000 55 >10000 >10000 >10000 >10000 59 >10000 >10000 >10000 >10000 60 >10000 >10000 >10000 >10000 61 >10000 >10000 >10000 >10000 62 >10000 >10000 >10000 >10000 90 >10000 >10000 >10000 >10000 91 >10000 >10000 >10000 >10000 92 >10000 >10000 >10000 >10000 213 >10000 >10000 >10000 >10000 131 >10000 >10000 >10000 >10000 145 >10000 >10000 >10000 >10000 157 >10000 >10000 >10000 >10000 176 >10000 >10000 >10000 >10000 226 >10000 >10000 >10000 >10000 227 >10000 >10000 >10000 >10000 228 >10000 >10000 >10000 >10000 229 >10000 >10000 >10000 >10000 231 >10000 >10000 >10000 >10000 232 >10000 >10000 >10000 >10000 233 >10000 >10000 >10000 >10000 234 >10000 >10000 >10000 >10000 235 >10000 >10000 >10000 >10000 242 >10000 >10000 >10000 >10000 243 >10000 >10000 >10000 >10000 277 >10000 >10000 >10000 >10000 355 >10000 >10000 >10000 >10000 365 >10000 >10000 >10000 >10000 381 >10000 >10000 >10000 >10000 390 >10000 >10000 >10000 >10000 398 >10000 >10000 >10000 >10000 400 >10000 >10000 >10000 >10000 437 >10000 >10000 >10000 >10000 

1. A compound of formula (I):

wherein: R¹ and R² are independently selected from H, OH, (C₁-C₁₀)alkyl, (C₁-C₆)alkoxy, (C₂-C₆)alkenyl, (C₃-C₁₀)cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aryl(C₁-C₄)alkyl- and heteroaryl(C₁-C₄)alkyl-; R³ is selected from H, (C₁-C₁₀)alkyl and (C₂-C₆)alkenyl; R⁴ and R⁵ are selected from H, (C₁-C₁₀)alkyl, (C₂-C₆)alkenyl, (C₃-C₁₀)cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aryl(C₁-C₄)alkyl- and heteroaryl(C₁-C₄)alkyl-; R⁶ and R⁷ are selected from H, (C₁-C₁₀)alkyl, (C₂-C₆)alkenyl, (C₃-C₁₀)cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aryl(C₁-C₄)alkyl-, aryl(C₂-C₄)alkenyl-, heteroaryl(C₁-C₄)alkyl-, —SO₂(C₁-C₆)alkyl, —SO₂aryl and —SO₂arylC₁-C₄)alkyl; or R⁶ and R⁷ together with the nitrogen atom to which they are attached may form a 4-7 membered N-containing ring, optionally containing one further heteroatom selected from N, O and S, and optionally substituted with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl, said N-containing ring may also optionally be fused to an aryl group; or R⁴ and R⁶ together with the atoms to which they are attached may form a saturated or partially unsaturated 4-7 membered N-containing ring, optionally containing one further heteroatom selected from N, O and S, and optionally substituted on carbon with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl; or R⁵ is absent and R⁴ and R⁶ together with the atoms to which they are attached may form a 5, 6, 9 or 10 membered mono- or bi-cyclic N-containing aromatic ring, optionally containing one further heteroatom selected from N, O and S, and optionally substituted on carbon with 1, 2 or 3 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN, aryl, COOR¹⁴ and hydroxyl; or R⁴ and R⁶ may together form a group according to formula II or formula III:

R⁸, R⁹ and R¹⁰ are independently selected from H, (C₁-C₁₀)alkyl, halo, hydroxyl and (C₁-C₆)alkoxy; R¹¹ is selected from H and (C₁-C₆)alkyl; R¹² is selected from H and (C₁-C₆)alkyl; R¹³ is selected from H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, OH, CN, CF₃, COOR¹⁴, halo and NR¹⁴R¹⁵; R¹⁴ and R¹⁵ are independently selected from H and (C₁-C₆)alkyl; f and g are independently selected from 0, 1, 2 and 3, such that f+g=1, 2 or 3; h is selected from 1 and 2; wherein: alkyl may optionally be substituted with 1 or 2 substituents independently selected from (C₃-C₁₀)cycloalkyl, (C₁-C₆)alkoxy, OH, CN, CF₃, COOR¹⁴, halo and NR¹⁴R¹⁵; alkenyl may optionally be substituted with 1 or 2 substituents independently selected from (C₃-C₁₀)cycloalkyl, (C₁-C₆)alkoxy, OH, CN, CF₃, COOR¹⁴, halo and NR¹⁴R¹⁵; alkoxy may optionally be substituted with 1 or 2 substituents independently selected from (C₃-C₁₀)cycloalkyl, OH, CN, CF₃, COOR¹⁴, halo and NR¹⁴ _(R) ¹⁵; cycloalkyl is a non-aromatic mono- or bi-cylic hydrocarbon ring, optionally fused to an aryl group, wherein said cycloalkyl ring optionally contains, where possible, up to 2 double bonds; and wherein, unless otherwise stated, said cycloalkyl may optionally be substituted with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, OH, CN, CF₃, COOR¹⁴ , halo and NR¹⁴R¹⁵; heterocycloalkyl is a C-linked or N-linked 3 to 10 membered non-aromatic, mono- or bi-cyclic ring, wherein said heterocycloalkyl ring contains, where possible, 1, 2 or 3 heteroatoms independently selected from N, NR¹⁴, S(O)_(q) and O; and said heterocycloalkyl ring optionally contains, where possible, 1 or 2 double bonds, and is optionally substituted on carbon with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, OH, CN, CF₃, halo, COOR¹⁴, NR¹⁴R¹⁵ and aryl; aryl is a single or fused aromatic ring system containing 6 or 10 carbon atoms; wherein, unless otherwise stated, each occurrence of aryl may be optionally substituted with up to 5 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, OH, halo, CN, COOR¹⁴, CF₃ and NR¹⁴R¹⁵; heteroaryl is a 5, 6, 9 or 10 membered mono- or bi-cyclic aromatic ring, containing 1 or 2 N atoms and, optionally, an NR¹⁴ atom, or one NR¹⁴ atom and an S or an O atom, or one S atom, or one O atom; wherein, unless otherwise stated, said heteroaryl may be optionally substituted with 1, 2 or 3 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, OH, halo, CN, COOR¹⁴, CF₃ and NR¹⁴R¹⁵; q is 0, 1 or 2; and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof.
 2. A compound according to claim 1, or a tautomer, stereoisomer, pharmaceutically acceptable salt or solvate thereof, wherein R¹ is selected from (C₁-C₁₀)alkyl, (C₃-C₁₀)cycloalkyl, aryl, heteroaryl and aryl(C₁-C₄)alkyl- and R² is selected from H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, OH, (C₃-C₁₀)cycloalkyl and aryl.
 3. A compound according to claim 1, or a tautomer, stereoisomer, pharmaceutically acceptable salt or solvate thereof, wherein R⁴ is selected from (C₁-C₁₀)alkyl, (C₃-C₁₀)cycloalkyl, aryl, heteroaryl, heteroaryl(C₁-C₄)alkyl- and aryl(C₁-C₄)alkyl- and R⁵ is selected from H and (C₁-C₆)alkyl.
 4. A compound according to claim 1, or a tautomer, stereoisomer, pharmaceutically acceptable salt or solvate thereof, wherein: R⁴ and R⁶ together with the atoms to which they are attached may form a 4-7 membered N-containing ring, optionally containing one carbon-carbon double bond, optionally containing one further heteroatom selected from N, O and S, and optionally substituted on carbon with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl; or R⁵ is absent and R⁴ and R⁶ together with the atoms to which they are attached may form a 5, 6 or 9 membered mono- or bi-cyclic N-containing aromatic ring, optionally containing one further heteroatom selected from N and O, and optionally substituted on carbon with 1, 2 or 3 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, aryl, COOR¹⁴ and hydroxyl; or R⁴ and R⁶ may together form a group according to formula II or formula III:

wherein R¹³ is H and f and g are independently selected from 0, 1, 2 and 3, such that f+g=1, 2 or 3; and h is selected from 1 and
 2. 5. A compound according to claim 1, or a tautomer, stereoisomer, pharmaceutically acceptable salt or solvate thereof, wherein R⁶ is selected from H and (C₁-C₆)alkyl, and R⁷ is selected from H, (C₁-C₁₀)alkyl, (C₃-C₁₀)cycloalkyl, aryl, heteroaryl, aryl(C₁-C₄)alkyl-, aryl(C₂-C₄)alkenyl-, heteroaryl(C₁-C₄)alkyl-, —SO₂(C₁-C₆)alkyl and —SO₂aryl.
 6. A compound according to claim 1, or a tautomer, stereoisomer, pharmaceutically acceptable salt or solvate thereof, wherein R⁶ and R⁷ together with the nitrogen atom to which they are attached may form a 5-6 membered N-containing ring, optionally containing one further heteroatom selected from N, O and S, and optionally substituted with 1 or 2 substituents independently selected from (C₁-C₆)alkyl, (C₁-C₆)alkoxy, halo, CN and hydroxyl, said N-containing ring may also optionally be fused to an aryl group.
 7. A compound according to claim 1, or a tautomer, stereoisomer, pharmaceutically acceptable salt or solvate thereof, wherein R⁸, R⁹ and R¹⁹ are independently selected from H, (C₁-C₁₀)alkyl and halogen, and R¹¹ and R¹² are H.
 8. A compound according to claim 1, selected from: (R)-1-Methyl-pyrrolidine-2-carboxylic acid {(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-naphthalen-1-yl-ethyl}-amide; (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-amide; (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; (R)-3-Methyl-2-methylamino-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,5-difluoro-phenyl)-ethyl]-amide; (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide; (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide; (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; (R)-1-Isopropyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide; (R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; (R)-1-Propyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; (R)-1-Isobutyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; (R)-1-Ethyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide; (S)—N-(6-Amino-pyridin-3-ylmethyl)-3-(3,4-difluoro-phenyl)-2-(2-diisopropylamino-acetylamino)-propionamide; (R)-1-Methyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; (R)-1-Methyl-piperidine-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide; (S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide; (R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; (R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-dimethylamino-3,3-dimethyl-butyramide; (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide; (R)-1-Methyl-pyrrolidine-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; (S)-1-Methyl-pyrrolidine-2-carboxylic acid {(R)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2,2-dicyclohexyl-ethyl}-amide; 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-fluoro-phenyl)-ethyl]-amide; 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide; 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-amide; 3-Methyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(4-fluoro-phenyl)-ethyl]-amide; 3,5-Dimethyl-1H-pyrrole-2-carboxylic acid [(S)-1-[(6-amino-2-methyl-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-amide; (R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl] -2-(3,4-dichloro-phenyl)-ethyl]-3-methyl-2-methylamino-butyramide; (S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-(ethyl-methyl-amino)-propionamide; (S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-difluoro-phenyl)-ethyl]-2-diethylamino-propionamide; (S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-(isopropyl-methyl-amino)-propionamide; (S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-cyclohexyl-ethyl}-2-diethylamino-propionamide; (S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(decahydro-naphthalen-1-yl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide; (R)-2-Dimethylamino-3-methyl-pentanoic acid [(S)-1-[(6-amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-amide; (R)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl]-2-dimethylamino-3-methyl-butyramide; (S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3,4-dichloro-phenyl)-ethyl-2-(isopropyl-methyl-amino)-propionamide; (S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-chloro-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide; (S)—N—{(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-m-tolyl-ethyl}-2-(isopropyl-methyl-amino)-propionamide; (S)—N—[(S)-1-[(6-Amino-pyridin-3-ylmethyl)-carbamoyl]-2-(3-trifluoromethyl-phenyl)-ethyl]-2-(isopropyl-methyl-amino)-propionamide; and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof.
 9. A method of treatment of a disease or condition in which KLK1 activity is implicated comprising administration to a subject in need thereof a therapeutically effective amount of a compound according to claim 1, or a tautomer, stereoisomer, pharmaceutically acceptable salt or solvate thereof.
 10. The method of claim 9 wherein the disease or condition in which KLK1 activity is implicated is selected from an inflammatory or respiratory disorder or condition selected from asthma (allergic and non-allergic), chronic obstructive pulmonary disease (COPD), allergic rhinitis (hayfever), cough, exacerbations resulting from asthma and chronic obstructive pulmonary disease (COPD), multiple sclerosis, arthritis, rheumatoid arthritis, osteopathic arthritis, osteoarthritis, rhinitis, sinusitis, inflammatory bowel disease (such as Crohn's disease and ulcerative colitis), immune mediated diabetes, acute pancreatitis and interstitial cystitis, conjunctivitis, periodontal disease, chronic prostate inflammation, chronic recurrent parotitis, inflammatory skin disorders (e.g. psoriasis, eczema), and SIRS (systemic inflammatory response syndrome); smooth muscle spasm (e.g. asthma, angina), RDS (respiratory distress syndrome), rhino-conjunctivitis, rhinorrhoea, urticaria or a neoplastic disorder.
 11. The method of claim 9 wherein the disease or condition in which KLK1 activity is implicated is selected from asthma (allergic and non-allergic), chronic obstructive pulmonary disease (COPD), allergic rhinitis (hayfever), cough, exacerbations resulting from asthma and chronic obstructive pulmonary disease (COPD),
 12. The method of claim 9 wherein the disease or condition in which KLK1 activity is implicated is selected from asthma (allergic and non-allergic) and cough.
 13. A pharmaceutical composition comprising a compound according to claim 1, or a tautomer, stereoisomer, pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 